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    Original research:

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    Original research:

    Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA).

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    • Review
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    • G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency.
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    • Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.
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    • Varsity Pharmaceuticals Licenses Pol-Theta Inhibitor From Dana-Farber Cancer Institute.
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    Original research:

    A first-in-class Polymerase Theta Inhibitor selectively targets Homologous-Recombination-Deficient Tumors.

    • Proteomic Analysis Reveals Low-Dose PARP Inhibitor-Induced Differential Protein Expression in BRCA1-Mutated High-Grade Serous Ovarian Cancer Cells.
    • Perez JM, Twigg CAI, Guan W, Thomas SN.
    • J Am Soc Mass Spectrom. 2022 Feb 2;33(2):242-250. doi: 10.1021/jasms.1c00215. Epub 2021 Dec 27.
    • Cell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissues.
    • Hsieh YP, Naler LB, Ma S, Lu C.
    • NAR Genom Bioinform. 2022 Feb 2;4(1):lqac006. doi: 10.1093/nargab/lqac006.
    • Therapeutic Targeting of DNA Damage Response in Cancer.
    • Choi W, Lee ES.
    • Int J Mol Sci. 2022 Feb 1;23(3):1701. doi: 10.3390/ijms23031701.
    • The DNA methylome of cervical cells can predict the presence of ovarian cancer.
    • Barrett JE, Jones A, Evans I, Reisel D, Herzog C, Chindera K, Kristiansen M, Leavy OC, Manchanda R, Bjørge L, Zikan M, Cibula D, Widschwendter M.
    • Nat Commun. 2022 Feb 1;13(1):448. doi: 10.1038/s41467-021-26615-y.

    Press: Methylation Signatures Within Cervical Cells Capture Ovarian, Breast Cancer Risk. (GenomeWeb)

    • The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples.
    • Barrett JE, Herzog C, Jones A, Leavy OC, Evans I, Knapp S, Reisel D, Nazarenko T, Kim YN, Franchi D, Ryan A, Franks J, Bjørge L, Zikan M, Cibula D, Harbeck N, Colombo N, Dudbridge F, Jones L, Sundström K, Dillner J, Rådestad AF, Gemzell-Danielsson K, Pashayan N, Widschwendter M.
    • Nat Commun. 2022 Feb 1;13(1):449. doi: 10.1038/s41467-021-27918-w.

    Press: Methylation Signatures Within Cervical Cells Capture Ovarian, Breast Cancer Risk. (GenomeWeb)

    • Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells.
    • Tadehara M, Kato T, Adachi K, Tamaki A, Kesen Y, Sakurai Y, Ichinoe M, Koizumi W, Murakumo Y.
    • Pancreas. 2022 Feb 1;51(2):183-189. doi: 10.1097/MPA.0000000000001975.
    • Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer.
    • Paffenholz SV, Salvagno C, Ho YJ, Limjoco M, Baslan T, Tian S, Kulick A, de Stanchina E, Wilkinson JE, Barriga FM, Zamarin D, Cubillos-Ruiz JR, Leibold J, Lowe SW.
    • Proc Natl Acad Sci U S A. 2022 Feb 1;119(5):e2117754119. doi: 10.1073/pnas.2117754119.

    Commentary:

    Platinum-based chemotherapy inflames the ovarian carcinoma microenvironment through cellular senescence.

    • Ovarian toxicity of carboplatin and paclitaxel in mouse carriers of mutation in BRIP1 tumor suppressor gene.
    • Ntemou E, Vidal PD, Alexandri C, Van den Steen G, Lambertini M, Demeestere I.
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    • Drug screening and genome editing in human pancreatic cancer organoids identifies drug-gene interactions and candidates for off-label treatment.
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    • Cell Genom. 2022 Feb;2(2):100095. doi: 10.1016/j.xgen.2022.100095.
    • Interaction of Wwox with Brca1 and associated complex proteins prevents premature resection at double-strand breaks and aberrant homologous recombination.
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    • A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders.
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    • Stakeholder attitudes towards establishing a national genomics registry of inherited cancer predisposition: a qualitative study.
    • Meiser B, Monnik M, Austin R, Nichols C, Cops E, Salmon L, Spurdle AB, Macrae F, Taylor N, Pachter N, James P, Kaur R.
    • J Community Genet. 2022 Feb;13(1):59-73. doi: 10.1007/s12687-021-00559-8. Epub 2021 Nov 2.
    • The BRCA2 missense mutation K2497R suppressed self-degradation and increased ATP production and cell proliferation.
    • Enkhbat G, Nakanishi A, Miki Y.
    • Biochem Biophys Res Commun. 2022 Jan 29;590:27-33. doi: 10.1016/j.bbrc.2021.12.073. Epub 2021 Dec 23.
    • Phenethyl Isothiocyanate Enhances the Cytotoxic Effects of PARP Inhibitors in High-Grade Serous Ovarian Cancer Cells.
    • Jia Y, Wang M, Sang X, Liu P, Gao J, Jiang K, Cheng H.
    • Front Oncol. 2022 Jan 26;11:812264. doi: 10.3389/fonc.2021.812264.
    • Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities.
    • Cosgrove N, Varešlija D, Keelan S, Elangovan A, Atkinson JM, Cocchiglia S, Bane FT, Singh V, Furney S, Hu C, Carter JM, Hart SN, Yadav S, Goetz MP, Hill ADK, Oesterreich S, Lee AV, Couch FJ, Young LS.
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    • DNA damage and repair in the hematopoietic system.
    • Li N, Chen H, Wang J.
    • Acta Biochim Biophys Sin (Shanghai). 2022 Jan 25. doi: 10.3724/abbs.2022053. Epub ahead of print.
    • CRL4-DCAF8L1 Regulates BRCA1 and BARD1 Protein Stability.
    • Liu F, Han Q, Zhang T, Chang F, Deng J, Huang X, Wang W, Xu Y, Li Q, Xu L, Zhang B, Li W, Li L, Su Y, Li Y, Shao G.
    • Int J Biol Sci. 2022 Jan 24;18(4):1434-1450. doi: 10.7150/ijbs.57178.
    • Inhibition of PKM2 Enhances Sensitivity of Olaparib to Ovarian Cancer Cells and Induces DNA Damage.
    • Zhou S, Li D, Xiao D, Wu T, Hu X, Zhang Y, Deng J, Long J, Xu S, Wu J, Li G, Peng M, Yang X.
    • Int J Biol Sci. 2022 Jan 24;18(4):1555-1568. doi: 10.7150/ijbs.62947.
    • Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma.
    • Kanakkanthara A, Hou X, Ekstrom TL, Zanfagnin V, Huehls AM, Kelly RL, Ding H, Larson MC, Vasmatzis G, Oberg AL, Kaufmann SH, Mansfield AS, Weroha SJ, Karnitz LM.
    • Cancer Res. 2022 Jan 15;82(2):307-319. doi: 10.1158/0008-5472.CAN-21-0732. Epub 2021 Nov 22.
    • CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival.
    • Minguillón J, Ramírez MJ, Rovirosa L, Bustamante-Madrid P, Camps-Fajol C, Ruiz de Garibay G, Shimelis H, Montanuy H, Pujol R, Hernandez G, Bogliolo M, Castillo P, Soucy P, Martrat G, Gómez A, Cuadras D, García MJ, Gayarre J, Cimba, Lázaro C, Benítez J, Couch FJ, Pujana MA, Surrallés J.
    • Cancers (Basel). 2022 Jan 12;14(2):353. doi: 10.3390/cancers14020353.
    • Harnessing Synthetic Lethal Interactions for Personalized Medicine.
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    • J Pers Med. 2022 Jan 12;12(1):98. doi: 10.3390/jpm12010098.
    • Construction and Validation of a Prognostic Risk Model for Triple Negative Breast Cancer Based on Autophagy-Related Genes.
    • Jia R, Yan C, Liu Q.
    • Front Oncol. 2022 Jan 10;10:829045. doi: 10.3389/fonc.2022.829045.
    • Disrupted BRCA1-PALB2 Interaction Induces Tumor Immunosuppression and T-Lymphocyte Infiltration in Hepatocellular Carcinoma Through cGAS-STING Pathway.
    • Ma H, Kang Z, Foo TK, Shen Z, Xia B.
    • Hepatology. 2022 Jan 10. doi: 10.1002/hep.32335. Epub ahead of print.
    • AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization.
    • Azzalini E, Tierno D, Bartoletti M, Barbazza R, Giorda G, Puglisi F, Cecere SC, Losito NS, Russo D, Stanta G, Canzonieri V, Bonin S.
    • Cancers (Basel). 2022 Jan 8;14(2):304. doi: 10.3390/cancers14020304.
    • Auger Emitter Conjugated PARP Inhibitor for Therapy in Triple Negative Breast Cancers: A Comparative In-Vitro Study.
    • Sankaranarayanan RA, Peil J, Vogg ATJ, Bolm C, Terhorst S, Classen A, Bauwens M, Maurer J, Mottaghy F, Morgenroth A.
    • Cancers (Basel). 2022 Jan 4;14(1):230. doi: 10.3390/cancers14010230.
    • A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer.
    • Park SJ, Chang SJ, Suh DH, Kong TW, Song H, Kim TH, Kim JW, Kim HS, Lee SJ.
    • BMC Cancer. 2022 Jan 3;22(1):28. doi: 10.1186/s12885-021-09138-z.
    • Mapping Intellectual Structures and Research Hotspots of Triple Negative Breast Cancer: A Bibliometric Analysis.
    • Hao KJ, Jia X, Dai WT, Huo ZM, Zhang HQ, Liu JW, Wang XB.
    • Front Oncol. 2022 Jan 3;11:689553. doi: 10.3389/fonc.2021.689553.
    • Molecular targeted drugs resistance impairs double-strand break repair and sensitizes ER-positive breast cancer to PARP inhibitors.
    • Suzuki Y, Wenwen W, Ohta T, Hayashi SI.
    • Breast Cancer. 2022 Jan;29(1):77-91. doi: 10.1007/s12282-021-01282-5. Epub 2021 Aug 3.
    • FDI-6 and olaparib synergistically inhibit the growth of pancreatic cancer by repressing BUB1, BRCA1 and CDC25A signaling pathways.
    • Wu SQ, Huang SH, Lin QW, Tang YX, Huang L, Xu YG, Wang SP.
    • Pharmacol Res. 2022 Jan;175:106040. doi: 10.1016/j.phrs.2021.106040. Epub 2021 Dec 22.
    • Multimodal immunostimulation to control BRCA1-defective ovarian carcinoma.
    • Klapp V, Galluzzi L.
    • Trends Cancer. 2022 Jan;8(1):1-3. doi: 10.1016/j.trecan.2021.11.006. Epub 2021 Nov 25.
    • Research news

    Original research:

    Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING.

    • Computational structural assessment of BReast CAncer type 1 susceptibility protein (BRCA1) and BRCA1-Associated Ring Domain protein 1 (BARD1) mutations on the protein-protein interface.
    • Thirumal Kumar D, Udhaya Kumar S, Jain N, Sowmya B, Balsekar K, Siva R, Kamaraj B, Sidenna M, George Priya Doss C, Zayed H.
    • Adv Protein Chem Struct Biol. 2022;130:375-397. doi: 10.1016/bs.apcsb.2022.02.003. Epub 2022 Apr 21.
    • Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer.
    • Garrido MP, Fredes AN, Lobos-González L, Valenzuela-Valderrama M, Vera DB, Romero C.
    • Biomedicines. 2021 Dec 31;10(1):77. doi: 10.3390/biomedicines10010077.
    • DNA Damage Repair: Predictor of Platinum Efficacy in Ovarian Cancer?
    • Stefanou DT, Souliotis VL, Zakopoulou R, Liontos M, Bamias A.
    • Biomedicines. 2021 Dec 31;10(1):82. doi: 10.3390/biomedicines10010082.
    • Dual targeting, a new strategy for novel PARP inhibitor discovery.
    • Wei L, Wang M, Wang Q, Han Z.
    • Drug Discov Ther. 2021 [Published: December 31, 2021];15(6):300-309. doi: 10.5582/ddt.2021.01100.
    • E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors.
    • Decourtye-Espiard L, Bougen-Zhukov N, Godwin T, Brew T, Schulpen E, Black MA, Guilford P.
    • Cancers (Basel). 2021 Dec 30;14(1):175. doi: 10.3390/cancers14010175.
    • Genetic Variation in MicroRNA-423 Promotes Proliferation, Migration, Invasion, and Chemoresistance in Breast Cancer Cells.
    • Morales-Pison S, Jara L, Carrasco V, Gutiérrez-Vera C, Reyes JM, Gonzalez-Hormazabal P, Carreño LJ, Tapia JC, Contreras HR.
    • Int J Mol Sci. 2021 Dec 29;23(1):380. doi: 10.3390/ijms23010380.
    • Human iPSC-derived fallopian tube organoids with BRCA1 mutation recapitulate early-stage carcinogenesis.
    • Yucer N, Ahdoot R, Workman MJ, Laperle AH, Recouvreux MS, Kurowski K, Naboulsi DJ, Liang V, Qu Y, Plummer JT, Gayther SA, Orsulic S, Karlan BY, Svendsen CN.
    • Cell Rep. 2021 Dec 28;37(13):110146. doi: 10.1016/j.celrep.2021.110146.

    Research news: Researchers Create Organoids that Model BRCA-Positive Ovarian Cancer. (Clinical OMICs)

    • BRCA2 Haploinsufficiency in Telomere Maintenance.
    • Gunnarsdottir SR, Bjarnason H, Thorvaldsdottir B, Paland F, Steinarsdottir M, Eyfjörd JE, Bödvarsdottir SK.
    • Genes (Basel). 2021 Dec 28;13(1):83. doi: 10.3390/genes13010083.
    • BRCA1 and Metastasis: Outcome of Defective DNA Repair.
    • Krishnan R, Patel PS, Hakem R.
    • Cancers (Basel). 2021 Dec 27;14(1):108. doi: 10.3390/cancers14010108.
    • Preventing and Overcoming Resistance to PARP Inhibitors: A Focus on the Clinical Landscape.
    • Prados-Carvajal R, Irving E, Lukashchuk N, Forment JV.
    • Cancers (Basel). 2021 Dec 23;14(1):44. doi: 10.3390/cancers14010044.
    • BRCA role changes with association: tissue-specific impact on the prognosis.
    • Gupta B, Somasundaram K.
    • Oncotarget. 2021 Dec 21;12(26):2541-2542. doi: 10.18632/oncotarget.28149.

    Original research:

    Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients.

    • LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells.
    • Xiang J, Zhou L, He Y, Wu S.
    • Aging (Albany NY). 2021 Dec 16;13(24):25920-25930. doi: 10.18632/aging.203780. Epub 2021 Dec 16.
    • Research Advances in the Role of the Poly ADP Ribose Polymerase Family in Cancer.
    • Sha H, Gan Y, Zou R, Wu J, Feng J.
    • Front Oncol. 2021 Dec 16;11:790967. doi: 10.3389/fonc.2021.790967.
    • Cockayne syndrome group B protein regulates fork restart, fork progression and MRE11-dependent fork degradation in BRCA1/2-deficient cells.
    • Batenburg NL, Mersaoui SY, Walker JR, Coulombe Y, Hammond-Martel I, Wurtele H, Masson JY, Zhu XD.
    • Nucleic Acids Res. 2021 Dec 16;49(22):12836-12854. doi: 10.1093/nar/gkab1173.
    • Loss of MED12 activates the TGFß pathway to promote chemoresistance and replication fork stability in BRCA-deficient cells.
    • Jackson LM, Dhoonmoon A, Hale A, Dennis KA, Schleicher EM, Nicolae CM, Moldovan GL.
    • Nucleic Acids Res. 2021 Dec 16;49(22):12855-12869. doi: 10.1093/nar/gkab1184.
    • Discovery of Potent and Novel Dual PARP/BRD4 Inhibitors for Efficient Treatment of Pancreatic Cancer.
    • Wang SP, Li Y, Huang SH, Wu SQ, Gao LL, Sun Q, Lin QW, Huang L, Meng LQ, Zou Y, Zhu QH, Xu YG.
    • J Med Chem. 2021 Dec 9;64(23):17413-17435. doi: 10.1021/acs.jmedchem.1c01535. Epub 2021 Nov 23.
    • Predictive Biomarkers of Immune Checkpoint Inhibitor Response in Breast Cancer: Looking beyond Tumoral PD-L1.
    • Chen N, Higashiyama N, Hoyos V.
    • Biomedicines. 2021 Dec 8;9(12):1863. doi: 10.3390/biomedicines9121863.
    • FDI-6 inhibits the expression and function of FOXM1 to sensitize BRCA-proficient triple-negative breast cancer cells to Olaparib by regulating cell cycle progression and DNA damage repair.
    • Wang SP, Wu SQ, Huang SH, Tang YX, Meng LQ, Liu F, Zhu QH, Xu YG.
    • Cell Death Dis. 2021 Dec 8;12(12):1138. doi: 10.1038/s41419-021-04434-9.
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    Commentary:

    When the RAP (80) fades out, you can hear BRCA1 RING.

    • A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive, recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial.
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    Commentary:

    Targeting BRCA-mutated tumors in mitosis.

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    Research news: Cancer Patients With BRCA1/2 Mutations Respond Differently to Immunotherapy, Study Shows. (Precision Oncology News; subscription required)

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    • Case report
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    • Review
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    • Review
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    • Review
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    • Review
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    Commentary:

    ASO Author Reflections: High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer.

    Commentary:

    ASO Visual Abstract: High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer.

    • Exome-Wide Pan-Cancer Analysis of Germline Variants in 8,719 Individuals Finds Little Evidence of Rare Variant Associations.
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    • Skeletal Muscle Function Is Dependent Upon BRCA1 to Maintain Genomic Stability.
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    •• Commentary:

    BRCA role changes with association: tissue-specific impact on the prognosis.

    •• Commentary:

    Redefining and expanding the sphere of influence of BRCA in breast and colorectal cancers and beyond.

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    News: Breast Cancer Genetic Risk Modified by Corticosteroid Use. (GenomeWeb)

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    • G-quadruplex DNA: a novel target for drug design.
    • Teng FY, Jiang ZZ, Guo M, Tan XZ, Chen F, Xi XG, Xu Y.
    • Cell Mol Life Sci. 2021 Aug 30. doi: 10.1007/s00018-021-03921-8. Epub ahead of print.
    • Review
    • Copper-Mediated Radiosynthesis of [18F]Rucaparib.
    • Chen Z, Destro G, Guibbal F, Chan CY, Cornelissen B, Gouverneur V.
    • Org Lett. 2021 Aug 30. doi: 10.1021/acs.orglett.1c02770. Epub ahead of print.
    • Discovery of First-in-Class Dual PARP and EZH2 Inhibitors for Triple-Negative Breast Cancer with Wild-Type BRCA.
    • Wang C, Qu L, Li S, Yin F, Ji L, Peng W, Luo H, Lu D, Liu X, Chen X, Kong L, Wang X.
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    • Uncovering cancer vulnerabilities by machine learning prediction of synthetic lethality.
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    • Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair.
    • Zahn KE, Jensen RB.
    • Genes (Basel). 2021 Aug 25;12(9):1310. doi: 10.3390/genes12091310.
    • Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer.
    • Long H, Hu X, Wang B, Wang Q, Wang R, Liu S, Xiong F, Jiang Z, Zhang XQ, Ye WC, Wang H.
    • J Med Chem. 2021 Aug 18. doi: 10.1021/acs.jmedchem.1c00735. Epub ahead of print.
    • Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay.
    • Nikoleousakos N, Dalezis P, Polonifi A, Geromichalou EG, Sagredou S, Alifieris CE, Deligiorgi MV, Sarli V, Trafalis DT.
    • Biomedicines. 2021 Aug 17;9(8):1028. doi: 10.3390/biomedicines9081028.
    • Recent Advances in Enhancing the Therapeutic Index of PARP Inhibitors in Breast Cancer.
    • Franchet C, Hoffmann JS, Dalenc F.
    • Cancers (Basel). 2021 Aug 17;13(16):4132. doi: 10.3390/cancers13164132.
    • Revisiting the BRCA-pathway through the lens of replication gap suppression: "Gaps determine therapy response in BRCA mutant cancer".
    • Cantor SB.
    • DNA Repair (Amst). 2021 Aug 13;107:103209. doi: 10.1016/j.dnarep.2021.103209. Epub ahead of print.
    • Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types.
    • Takamatsu S, Brown JB, Yamaguchi K, Hamanishi J, Yamanoi K, Takaya H, Kaneyasu T, Mori S, Mandai M, Matsumura N.
    • JCO Precis Oncol. 2021 Aug 11;5:PO.21.00141. doi: 10.1200/PO.21.00141.
    • The Fanconi anemia pathway and Breast Cancer: A comprehensive review of clinical data.
    • Gianni P, Matenoglou E, Geropoulos G, Agrawal N, Adnani H, Zafeiropoulos S, Miyara SJ, Guevara S, Mumford JM, Molmenti EP, Giannis D.
    • Clin Breast Cancer. 2021 Aug 10:S1526-8209(21)00238-X. doi: 10.1016/j.clbc.2021.08.001. Epub ahead of print.
    • Review
    • Revealing biomarkers associated with PARP inhibitors based on genetic interactions in cancer genome.
    • Dong Q, Liu M, Chen B, Zhao Z, Chen T, Wang C, Zhuang S, Li Y, Wang Y, Ai L, Liu Y, Liang H, Qi L, Gu Y.
    • Comput Struct Biotechnol J. 2021 Aug 10;19:4435-4446. doi: 10.1016/j.csbj.2021.08.007.
    • CEACAM Gene Family Mutations Associated With Inherited Breast Cancer Risk - A Comparative Oncology Approach to Discovery.
    • Huskey ALW, McNeely I, Merner ND.
    • Front Genet. 2021 Aug 10;12:702889. doi: 10.3389/fgene.2021.702889.
    • Guardians of the Genome: BRCA2 and Its Partners.
    • Le HP, Heyer WD, Liu J.
    • Genes (Basel). 2021 Aug 10;12(8):1229. doi: 10.3390/genes12081229.
    • Anticancer activity of RAPTA-EA1 in triple-negative BRCA1 proficient breast cancer cells: single and combined treatment with the PARP inhibitor olaparib.
    • Hongthong K, Nhukeaw T, Temboot P, Dyson PJ, Ratanaphan A.
    • Heliyon. 2021 Aug 10;7(8):e07749. doi: 10.1016/j.heliyon.2021.e07749.
    • PARP Inhibitors Display Differential Efficacy in Models of BRCA Mutant High-Grade Serous Ovarian Cancer.
    • Dickson KA, Xie T, Evenhuis C, Ma Y, Marsh DJ.
    • Int J Mol Sci. 2021 Aug 7;22(16):8506. doi: 10.3390/ijms22168506.
    • Subclone eradication analysis identifies targets for enhanced cancer therapy and reveals L1 retrotransposition as a dynamic source of cancer heterogeneity.
    • Ketola K, Kaljunen H, Taavitsainen S, Kaarijärvi R, Järvelä E, Rodriguez Martin B, Haase K, Woodcock DJ, Tubio J, Wedge DC, Nykter M, Bova GS.
    • Cancer Res. 2021 Aug 4:canres.0371.2021. doi: 10.1158/0008-5472.CAN-21-0371. Epub ahead of print.
    • BRCA2 deficiency reveals that oxidative stress impairs RNaseH1 function to cripple mitochondrial DNA maintenance.
    • Renaudin X, Lee M, Shehata M, Surmann EM, Venkitaraman AR.
    • Cell Rep. 2021 Aug 3;36(5):109478. doi: 10.1016/j.celrep.2021.109478.
    • PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in mice.
    • Bosnjak M, Jesenko T, Markelc B, Janzic L, Cemazar M, Sersa G.
    • Bioelectrochemistry. 2021 Aug;140:107832. doi: 10.1016/j.bioelechem.2021.107832. Epub 2021 May 1. Erratum in: Bioelectrochemistry. 2021 Oct;141:107865.
    • MAPK4 silencing together with a PARP1 inhibitor as a combination therapy in triple-negative breast cancer cells.
    • Zeng X, Jiang S, Ruan S, Guo Z, Guo J, Liu M, Ye C, Dong J.
    • Mol Med Rep. 2021 Aug;24(2):548. doi: 10.3892/mmr.2021.12187. Epub 2021 Jun 3.
    • Acquired RAD51C promoter methylation loss causes PARP inhibitor resistance in high grade serous ovarian carcinoma.
    • Nesic K, Kondrashova O, Hurley RM, McGehee CD, Vandenberg CJ, Ho GY, Lieschke E, Dall G, Bound N, Shield-Artin K, Radke M, Musafer A, Chai ZQ, Eftekhariyan Ghamsari MR, Harrell MI, Kee D, Olesen I, McNally O, Traficante N, Cancer Study AO, DeFazio A, Bowtell DDL, Swisher EM, Weroha SJ, Nones K, Waddell N, Kaufmann SH, Dobrovic A, Wakefield MJ, Scott CL.
    • Cancer Res. 2021 Jul 28:canres.0774.2021. doi: 10.1158/0008-5472.CAN-21-0774. Epub ahead of print.
    • Selective progesterone receptor blockade prevents BRCA1-associated mouse mammary tumors through modulation of epithelial and stromal genes.
    • Lee O, Bosland MC, Wang M, Shidfar A, Hosseini O, Xuei X, Patel P, Schipma MJ, Helenowski I, Kim JJ, Clare SE, Khan SA.
    • Cancer Lett. 2021 Jul 27:S0304-3835(21)00361-X. doi: 10.1016/j.canlet.2021.07.034. Epub ahead of print.
    • ATR/ATM-mediated phosphorylation of BRCA1 T1394 promotes homologous recombinational repair and G2/M checkpoint maintenance.
    • Foo TK, Vincelli G, Huselid E, Her J, Zheng H, Simhadri S, Wang M, Huo Y, Li T, Yu X, Li H, Zhao W, Bunting SF, Xia B.
    • Cancer Res. 2021 Jul 23:canres.2723.2020. doi: 10.1158/0008-5472.CAN-20-2723. Epub ahead of print.
    • Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants.
    • Macchini M, Centonze F, Peretti U, Orsi G, Militello AM, Valente MM, Cascinu S, Reni M.
    • Cancer Treat Rev. 2021 Jul 23;100:102262. doi: 10.1016/j.ctrv.2021.102262. Epub ahead of print.
    • Review
    • Increased gene expression variability in BRCA1-associated and basal-like breast tumours.
    • Wiggins GAR, Black MA, Dunbier A, Morley-Bunker AE; kConFab Investigators, Pearson JF, Walker LC.
    • Breast Cancer Res Treat. 2021 Jul 21. doi: 10.1007/s10549-021-06328-y. Epub ahead of print.
    • BRCA2 Promotes Spontaneous Homologous Recombination In Vivo.
    • Brown AD, Greenman S, Claybon AB, Bishop AJR.
    • Cancers (Basel). 2021 Jul 21;13(15):3663. doi: 10.3390/cancers13153663.
    • Intrinsic Disorder and Phosphorylation in BRCA2 Facilitate Tight Regulation of Multiple Conserved Binding Events.
    • Julien M, Ghouil R, Petitalot A, Caputo SM, Carreira A, Zinn-Justin S.
    • Biomolecules. 2021 Jul 20;11(7):1060. doi: 10.3390/biom11071060.
    • Cell-autonomous inflammation of BRCA1-deficient ovarian cancers drives both tumor-intrinsic immunoreactivity and immune resistance via STING.
    • Bruand M, Barras D, Mina M, Ghisoni E, Morotti M, Lanitis E, Fahr N, Desbuisson M, Grimm A, Zhang H, Chong C, Dagher J, Chee S, Tsianou T, Dorier J, Stevenson BJ, Iseli C, Ronet C, Bobisse S, Genolet R, Walton J, Bassani-Sternberg M, Kandalaft LE, Ren B, McNeish I, Swisher E, Harari A, Delorenzi M, Ciriello G, Irving M, Rusakiewicz S, Foukas PG, Martinon F, Dangaj Laniti D, Coukos G.
    • Cell Rep. 2021 Jul 20;36(3):109412. doi: 10.1016/j.celrep.2021.109412.

    Research news:

    Multimodal immunostimulation to control BRCA1-defective ovarian carcinoma.

    • Prediction of BRCA Gene Mutation in Breast Cancer Based on Deep Learning and Histopathology Images.
    • Wang X, Zou C, Zhang Y, Li X, Wang C, Ke F, Chen J, Wang W, Wang D, Xu X, Xie L, Zhang Y.
    • Front Genet. 2021 Jul 20;12:661109. doi: 10.3389/fgene.2021.661109.
    • Involvement of ATMIN-DYNLL1-MRN axis in the progression and aggressiveness of serous ovarian cancer.
    • Berkel C, Cacan E.
    • Biochem Biophys Res Commun. 2021 Jul 14;570:74-81. doi: 10.1016/j.bbrc.2021.07.004. Epub ahead of print.
    • A computational and structural analysis of germline and somatic variants affecting the DDR mechanism, and their impact on human diseases.
    • Magraner-Pardo L, Laskowski RA, Pons T, Thornton JM.
    • Sci Rep. 2021 Jul 12;11(1):14268. doi: 10.1038/s41598-021-93715-6.
    • Suppression of DNA Polymerase ß Activity Is Synthetically Lethal in BRCA1-Deficient Cells.
    • Yuhas SC, Mishra A, DeWeese TL, Greenberg MM.
    • ACS Chem Biol. 2021 Jul 9. doi: 10.1021/acschembio.1c00385. Epub ahead of print.
    • Electronic characteristics of BRCA1 mutations in DNA.
    • He L, Zhang J, He C, Zhao B, Xie Z, Chen W, Sonawane MR, Patil SR.
    • Biopolymers. 2021 Jul 9:e23465. doi: 10.1002/bip.23465. Epub ahead of print.
    • Characterization of a RAD51C-silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance.
    • Hurley RM, McGehee CD, Nesic K, Correia C, Weiskittel TM, Kelly RL, Venkatachalam A, Hou X, Pathoulas NM, Meng XW, Kondrashova O, Radke MR, Schneider PA, Flatten KS, Peterson KL, Becker MA, Wong EM, Southey MS, Dobrovic A, Lin KK, Harding TC, McNeish I, Ross CA, Wagner JM, Wakefield MJ, Scott CL, Haluska P, Wahner Hendrickson AE, Karnitz LM, Swisher EM, Li H, Weroha SJ, Kaufmann SH.
    • NAR Cancer. 2021 Jul 9;3(3):zcab028. doi: 10.1093/narcan/zcab028.
    • Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.
    • Kar SP, Considine DPC, Tyrer JP, Plummer JT, Chen S, Dezem FS, Barbeira AN, Rajagopal PS, Rosenow WT, Moreno F, Bodelon C, Chang-Claude J, Chenevix-Trench G, deFazio A, Dörk T, Ekici AB, Ewing A, Fountzilas G, Goode EL, Hartman M, Heitz F, Hillemanns P, Høgdall E, Høgdall CK, Huzarski T, Jensen A, Karlan BY, Khusnutdinova E, Kiemeney LA, Kjaer SK, Klapdor R, Köbel M, Li J, Liebrich C, May T, Olsson H, Permuth JB, Peterlongo P, Radice P, Ramus SJ, Riggan MJ, Risch HA, Saloustros E, Simard J, Szafron LM, Titus L, Thompson CL, Vierkant RA, Winham SJ, Zheng W, Doherty JA, Berchuck A, Lawrenson K, Im HK, Manichaikul AW, Pharoah PDP, Gayther SA, Schildkraut JM.
    • HGG Adv. 2021 Jul 8;2(3):100042. doi: 10.1016/j.xhgg.2021.100042. Epub 2021 Jun 16.
    • Analysis of adaptive olaparib resistance effects on cisplatin sensitivity in triple negative breast cancer cells.
    • Gajan A, Sarma A, Kim S, Gurdziel K, Wu GS, Shekhar M.
    • Front Oncol. 2021 Jul 5. doi: 10.3389/fonc.2021.694793.
    • Dual PARP and RAD51 Inhibitory Drug Conjugates Show Synergistic and Selective Effects on Breast Cancer Cells.
    • Malka MM, Eberle J, Niedermayer K, Zlotos DP, Wiesmüller L.
    • Biomolecules. 2021 Jul 3;11(7):981. doi: 10.3390/biom11070981.
    • Changes in Stem Cell Regulation and Epithelial Organisation during Carcinogenesis and Disease Progression in Gynaecological Malignancies.
    • Cunnea P, Fotopoulou C, Ploski J, Trillsch F, Mahner S, Kessler M.
    • Cancers (Basel). 2021 Jul 3;13(13):3349. doi: 10.3390/cancers13133349.
    • Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses.
    • Andreassen PR, Seo J, Wiek C, Hanenberg H.
    • Genes (Basel). 2021 Jul 2;12(7):1034. doi: 10.3390/genes12071034.
    • Design, Synthesis and Activity Evaluation of New Phthalazinone PARP Inhibitors.
    • Huang M, Ren J, Wang Y, Chen X, Yang J, Tang T, Yang Z, Li X, Ji M, Cai J.
    • Chem Pharm Bull (Tokyo). 2021 [Jul 1];69(7):620-629. doi: 10.1248/cpb.c20-01018.
    • Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2.
    • Tang M, Pei G, Su D, Wang C, Feng X, Srivastava M, Chen Z, Zhao Z, Chen J.
    • Nucleic Acids Res. 2021 Jul 1:gkab540. doi: 10.1093/nar/gkab540. Epub ahead of print.
    • Soluble interleukin-2 receptor as a predictive and prognostic marker for patients with familial breast cancer.
    • Gonda K, Horita S, Maejima Y, Takenoshita S, Shimomura K.
    • Sci Prog. 2021 Jul-Sep;104(3):368504211039590. doi: 10.1177/00368504211039590.
    • Identifying patients eligible for PARP inhibitor treatment: from NGS-based tests to 3D functional assays.
    • Morice PM, Coquan E, Weiswald LB, Lambert B, Vaur D, Poulain L.
    • Br J Cancer. 2021 Jul;125(1):7-14. doi: 10.1038/s41416-021-01295-z. Epub 2021 Mar 25.
    • Commentary, Review
    • BRCA1/2 signaling and homologous recombination deficiency in breast and ovarian cancer.
    • Royfman R, Whiteley E, Noe O, Morand S, Creeden J, Stanbery L, Hamouda D, Nemunaitis J.
    • Future Oncol. 2021 Jul;17(21):2817-2830. doi: 10.2217/fon-2021-0072. Epub 2021 Jun 1.
    • Review
    • RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers.
    • Reye G, Huang X, Britt KL, Meinert C, Blick T, Xu Y, Momot KI, Lloyd T, Northey JJ, Thompson EW, Hugo HJ.
    • Cancers (Basel). 2021 Jun 29;13(13):3251. doi: 10.3390/cancers13133251.
    • Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency.
    • Cong K, Peng M, Kousholt AN, Lee WTC, Lee S, Nayak S, Krais J, VanderVere-Carozza PS, Pawelczak KS, Calvo J, Panzarino NJ, Jonkers J, Johnson N, Turchi JJ, Rothenberg E, Cantor SB.
    • Mol Cell. 2021 Jun 26:S1097-2765(21)00458-5. doi: 10.1016/j.molcel.2021.06.011. Epub ahead of print.
    • BARD1 Autoantibody Blood Test for Early Detection of Ovarian Cancer.
    • Pilyugin M, Ratasjka M, Maciej Stukan M, Concin N, Zeillinger R, Irminger-Finger I.
    • Genes (Basel). 2021 Jun 25;12(7):969. doi: 10.3390/genes12070969.
    • The Effects of Chemotherapeutics on the Ovarian Cancer Microenvironment.
    • Eckert MA, Orozco C, Xiao J, Javellana M, Lengyel E.
    • Cancers (Basel). 2021 Jun 23;13(13):3136. doi: 10.3390/cancers13133136.
    • Pfizer Studying Talzenna in Advanced Prostate Cancer Patients With DNA Damage Response Gene Defects.
    • [No author given]
    • Precision Oncology News. Cancer Specialties. Prostate Cancer. 2021 Jun 23.
    • Platelet-Activating Factor Acetylhydrolase Expression in BRCA1 Mutant Ovarian Cancer as a Protective Factor and Potential Negative Regulator of the Wnt Signaling Pathway.
    • Liao Y, Badmann S, Kaltofen T, Mayr D, Schmoeckel E, Deuster E, Mannewitz M, Landgrebe S, Kolben T, Hester A, Beyer S, Burges A, Mahner S, Jeschke U, Trillsch F, Czogalla B.
    • Biomedicines. 2021 Jun 22;9(7):706. doi: 10.3390/biomedicines9070706.
    • Nuclear Export Inhibitor KPT-8602 Synergizes with PARP Inhibitors in Escalating Apoptosis in Castration Resistant Cancer Cells.
    • Uddin MH, Li Y, Khan HY, Muqbil I, Aboukameel A, Sexton RE, Reddy S, Landesman Y, Kashyap T, Azmi AS, Heath EI.
    • Int J Mol Sci. 2021 Jun 22;22(13):6676. doi: 10.3390/ijms22136676.
    • Synthesis and evaluation of 2-(4-[4-acetylpiperazine-1-carbonyl] phenyl)-1H-benzo[d]imidazole-4-carboxamide derivatives as potential PARP-1 inhibitors and preliminary study on structure-activity relationship.
    • Chen M, Huang H, Wu K, Liu Y, Jiang L, Li Y, Tang G, Peng J, Cao X.
    • Drug Dev Res. 2021 Jun 21. doi: 10.1002/ddr.21843. Epub ahead of print.
    • Risk of epithelial ovarian cancer Type I and II after hysterectomy, salpingectomy and tubal ligation - A nationwide case control study.
    • Darelius A, Kristjansdottir B, Dahm-Kähler P, Strandell A.
    • Int J Cancer. 2021 Jun 21. doi: 10.1002/ijc.33714. Epub ahead of print.
    • The RAD51-FFPE Test; Calibration of a Functional Homologous Recombination Deficiency Test on Diagnostic Endometrial and Ovarian Tumor Blocks.
    • van Wijk LM, Kramer CJH, Vermeulen S, ter Haar NT, de Jonge MM, Kroep JR, de Kroon CD, Gaarenstroom KN, Vrieling H, Bosse T, Vreeswijk MPG.
    • Cancers (Basel). 2021 Jun 18;13(12):2994. doi: 10.3390/cancers13122994.
    • Breast specific molecular clocks comprised of ELF5 expression and promoter methylation identify individuals susceptible to cancer initiation.
    • Miyano M, Sayaman RW, Shalabi SF, Senapati P, Lopez JC, Angarola BL, Hinz S, Zirbes A, Anczukow O, Yee LD, Sedrak MS, Stampfer MR, Seewaldt VL, LaBarge MA.
    • Cancer Prev Res (Phila). 2021 Jun 17:canprevres.CAPR-20-0635-A.2020. doi: 10.1158/1940-6207.CAPR-20-0635. Epub ahead of print.
    • Comprehensive Landscape of Ovarian Cancer Immune Microenvironment Based on Integrated Multi-Omics Analysis.
    • Shen J, Liu T, Bei Q, Xu S.
    • Front Oncol. 2021 Jun 17;11:685065. doi: 10.3389/fonc.2021.685065.
    • Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
    • Zatreanu D, Robinson HMR, Alkhatib O, Boursier M, Finch H, Geo L, Grande D, Grinkevich V, Heald RA, Langdon S, Majithiya J, McWhirter C, Martin NMB, Moore S, Neves J, Rajendra E, Ranzani M, Schaedler T, Stockley M, Wiggins K, Brough R, Sridhar S, Gulati A, Shao N, Badder LM, Novo D, Knight EG, Marlow R, Haider S, Callen E, Hewitt G, Schimmel J, Prevo R, Alli C, Ferdinand A, Bell C, Blencowe P, Bot C, Calder M, Charles M, Curry J, Ekwuru T, Ewings K, Krajewski W, MacDonald E, McCarron H, Pang L, Pedder C, Rigoreau L, Swarbrick M, Wheatley E, Willis S, Wong AC, Nussenzweig A, Tijsterman M, Tutt A, Boulton SJ, Higgins GS, Pettitt SJ, Smith GCM, Lord CJ.
    • Nat Commun. 2021 Jun 17;12(1):3636. doi: 10.1038/s41467-021-23463-8.
    • Association between Predicted Effects of TP53 Missense Variants on Protein Conformation and Their Phenotypic Presentation as Li-Fraumeni Syndrome or Hereditary Breast Cancer.
    • Liu Y, Axell O, van Leeuwen T, Konrat R, Kharaziha P, Larsson C, Wright APH, Bajalica-Lagercrantz S.
    • Int J Mol Sci. 2021 Jun 14;22(12):6345. doi: 10.3390/ijms22126345.
    • Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy?
    • Orhan E, Velazquez C, Tabet I, Sardet C, Theillet C.
    • Cancers (Basel). 2021 Jun 11;13(12):2930. doi: 10.3390/cancers13122930.
    • Helicobacter pylori CagA elicits BRCAness to induce genome instability that may underlie bacterial gastric carcinogenesis.
    • Imai S, Ooki T, Murata-Kamiya N, Komura D, Tahmina K, Wu W, Takahashi-Kanemitsu A, Knight CT, Kunita A, Suzuki N, Del Valle AA, Tsuboi M, Hata M, Hayakawa Y, Ohnishi N, Ueda K, Fukayama M, Ushiku T, Ishikawa S, Hatakeyama M.
    • Cell Host Microbe. 2021 Jun 9;29(6):941-958.e10. doi: 10.1016/j.chom.2021.04.006. Epub 2021 May 13.
    • PARP inhibitors promote stromal fibroblast activation by enhancing CCL5 autocrine signaling in ovarian cancer.
    • Li X, Fang T, Xu S, Jin P, Zhou D, Wang Z, Li H, Yang Z, Chen G, Zheng X, Xia Y, Wei X, Zhang Z, Yang X, Wang Y, Gao Q.
    • NPJ Precis Oncol. 2021 Jun 9;5(1):49. doi: 10.1038/s41698-021-00189-w.
    • Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA.
    • Sumanasuriya S, Seed G, Parr H, Christova R, Pope L, Bertan C, Bianchini D, Rescigno P, Figueiredo I, Goodall J, Fowler G, Flohr P, Mehra N, Neeb A, Rekowski J, Eisenberger M, Sartor O, Oudard S, Geffriaud-Ricouard C, Ozatilgan A, Chadjaa M, Macé S, Lord C, Baxter J, Pettitt S, Lambros M, Sharp A, Mateo J, Carreira S, Yuan W, de Bono JS.
    • Eur Urol. 2021 Jun 5:S0302-2838(21)01799-1. doi: 10.1016/j.eururo.2021.05.030. Epub ahead of print.
    • Cancer-causing BRCA2 missense mutations disrupt an intracellular protein assembly mechanism to disable genome maintenance.
    • Lee M, Shorthouse D, Mahen R, Hall BA, Venkitaraman AR.
    • Nucleic Acids Res. 2021 Jun 4;49(10):5588-5604. doi: 10.1093/nar/gkab308.
    • The Fanconi anemia ubiquitin E3 ligase complex as an anti-cancer target.
    • Sharp MF, Bythell-Douglas R, Deans AJ, Crismani W.
    • Mol Cell. 2021 Jun 3;81(11):2278-2289. doi: 10.1016/j.molcel.2021.04.023. Epub 2021 May 12.
    • Review
    • BRCA1-BRCT Mutations Alter the Subcellular Localization of BRCA1 In Vitro.
    • Drikos I, Boutou E, Kastritis PL, Vorgias CE.
    • Anticancer Res. 2021 Jun;41(6):2953-2962. doi: 10.21873/anticanres.15077.
    • Enhancing the sensitivity of ovarian cancer cells to olaparib via microRNA-20b-mediated cyclin D1 targeting.
    • Zhong Q, Xiong Y, Ling C, Qian Y, Zhao X, Yang H.
    • Exp Biol Med (Maywood). 2021 Jun;246(11):1297-1306. doi: 10.1177/1535370221994077.
    • A first-in-class Polymerase Theta Inhibitor selectively targets Homologous-Recombination-Deficient Tumors.
    • Zhou J, Gelot C, Pantelidou C, Li A, Yücel H, Davis RE, Färkkilä A, Kochupurakkal B, Syed A, Shapiro GI, Tainer JA, Blagg BSJ, Ceccaldi R, D'Andrea AD.
    • Nat Cancer. 2021 Jun;2(6):598-610. doi: 10.1038/s43018-021-00203-x. Epub 2021 Jun 17.

    Press: Old Antibiotic Targets BRCA-Mutated, PARP Inhibitor-Resistant Tumors (Clinical OMICs)

    • PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer.
    • Hong T, Lei G, Chen X, Li H, Zhang X, Wu N, Zhao Y, Zhang Y, Wang J.
    • Redox Biol. 2021 Jun;42:101928. doi: 10.1016/j.redox.2021.101928. Epub 2021 Mar 5.
    • Breast cancer type 1 and neurodegeneration: consequences of deficient DNA repair.
    • Leung E, Hazrati LN.
    • Brain Commun. 2021 May 27;3(2):fcab117. doi: 10.1093/braincomms/fcab117.
    • The role of PARP inhibitors in the ovarian cancer microenvironment; moving forward from synthetic lethality.
    • Turinetto M, Scotto G, Tuninetti V, Giannone G, Valabrega G.
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    • Synergistic Effect of Bazedoxifene and PARP Inhibitor in the Treatment of Ovarian Cancer Regardless of BRCA Mutation.
    • Zhang R, Wang T, Lin J.
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    • Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue-specific carcinogenesis.
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    • Generation and characterization of induced pluripotent stem cells heterozygous for the Portuguese BRCA2 founder mutation.
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    • Identification of a RAD52 Inhibitor Inducing Synthetic Lethality in BRCA2-Deficient Cancer Cells.
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    • Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging.
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    • DDX11 loss causes replication stress and pharmacologically exploitable DNA repair defects.
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    • BBIT20 inhibits homologous DNA repair with disruption of the BRCA1-BARD1 interaction in breast and ovarian cancer.
    • Raimundo L, Paterna Â, Calheiros J, Ribeiro J, Cardoso D, Piga I, Neto SJ, Hegan D, Glazer PM, Indraccolo S, Mulhovo S, Costa JL, Ferreira MU, Saraiva L.
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    • The PARP Enzyme Family and the Hallmarks of Cancer Part 2: Hallmarks Related to Cancer Host Interactions.
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    • Functional Genomic Analyses of the 21q22.3 Locus Identifying Functional Variants and Candidate Gene YBEY for Breast Cancer Risk.
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    • The PARP Enzyme Family and the Hallmarks of Cancer Part 1. Cell Intrinsic Hallmarks.
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    • BRCA1 and BRCA2 Tumor Suppressor Function in Meiosis.
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    • Otsuka I.
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    • Genetic interactions among Brca1, Brca2, Palb2, and Trp53 in mammary tumor development.
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    • NPJ Breast Cancer. 2021 Apr 23;7(1):45. doi: 10.1038/s41523-021-00253-5.
    • CHK2 inhibition provides a strategy to suppress hematological toxicity from PARP inhibitors.
    • Xu Z, Vandenberg CJ, Lieschke E, Di Rago L, Scott CL, Majewski IJ.
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    • FEN1 Blockade for Platinum Chemo-Sensitization and Synthetic Lethality in Epithelial Ovarian Cancers.
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    • A new interaction between BRCA2 and DDX5 promotes the repair of DNA breaks at transcribed chromatin.
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    • Commentary
    • In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer.
    • Lin ZP, Al Zouabi NN, Xu ML, Bowen NE, Wu TL, Lavi ES, Huang PH, Zhu YL, Kim B, Ratner ES.
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    • WNT inhibition creates a BRCA-like state in Wnt-addicted cancer.
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    • Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors.
    • Fugger K, Bajrami I, Silva Dos Santos M, Young SJ, Kunzelmann S, Kelly G, Hewitt G, Patel H, Goldstone R, Carell T, Boulton SJ, MacRae J, Taylor IA, West SC.
    • Science. 2021 Apr 9;372(6538):156-165. doi: 10.1126/science.abb4542.

    Comment:

    Epigenetic nucleotides enhance therapy.

    • Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer.
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    • The dystonia gene THAP1 controls DNA double-strand break repair choice.
    • Shinoda K, Zong D, Callen E, Wu W, Dumitrache LC, Belinky F, Chari R, Wong N, Ishikawa M, Stanlie A, Multhaupt-Buell T, Sharma N, Ozelius L, Ehrlich M, McKinnon PJ, Nussenzweig A.
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    • Synthetic Lethality in Cancer Therapeutics: The Next Generation.
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    • Cancer Discov. 2021 Apr 1. doi: 10.1158/2159-8290.CD-20-1503. Epub ahead of print.
    • Review
    • Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation.
    • Fontelles CC, da Cruz RS, Gonsiewski AK, Barin E, Tekmen V, Jin L, Cruz MI, Loudig O, Warri A, de Assis S.
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    • Molecular disruption of DNA polymerase ß for platinum sensitisation and synthetic lethality in epithelial ovarian cancers.
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    • Oncogene. 2021 Apr;40(14):2496-2508. doi: 10.1038/s41388-021-01710-y. Epub 2021 Mar 5.
    • Exploiting synthetic lethality to target BRCA1/2-deficient tumors: where we stand.
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    • Review
    • Structure analysis of deleterious nsSNPs in human PALB2 protein for functional inference.
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    • Bioinformation. 2021 Mar 31;17(3):424-438. doi: 10.6026/97320630017424.
    • Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival.
    • Earl J, Barreto E, Castillo ME, Fuentes R, Rodríguez-Garrote M, Ferreiro R, Reguera P, Muñoz G, Garcia-Seisdedos D, López JV, Sainz B Jr, Malats N, Carrato A.
    • Cancers (Basel). 2021 Mar 31;13(7):1612. doi: 10.3390/cancers13071612. Erratum in: Cancers (Basel). 2021 Jul 22;13(15):3687.
    • Determinants of serum adiponectin levels: a cross-sectional study.
    • Sattarinezhad A, Rasekhi Kazerouni A, Omrani GR, Shams M.
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    • Decreased expression of the translation factor eIF3e induces senescence in breast cancer cells via suppression of PARP1 and activation of mTORC1.
    • Morris C, Durand S, Jalinot P.
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    • Selective killing of homologous recombination-deficient cancer cell lines by inhibitors of the RPA:RAD52 protein-protein interaction.
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    • Alteration of DNA Damage Response Causes Cleft Palate.
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    • Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts.
    • Martin M, Ramos-Medina R, Bernat R, García-Saenz JA, Del Monte-Millan M, Alvarez E, Cebollero M, Moreno F, Gonzalez-Haba E, Bueno O, Romero P, Massarrah T, Echavarria I, Jerez Y, Herrero B, Gonzalez Del Val R, Lobato N, Rincon P, Palomero MI, Marquez-Rodas I, Lizarraga S, Asensio F, Lopez-Tarruella S.
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    • SP142 PD-L1 Scoring Shows High Interobserver and Intraobserver Agreement in Triple-negative Breast Carcinoma But Overall Low Percentage Agreement With Other PD-L1 Clones SP263 and 22C3.
    • Pang JB, Castles B, Byrne DJ, Button P, Hendry S, Lakhani SR, Sivasubramaniam V, Cooper WA, Armes J, Millar EKA, Raymond W, Roberts-Thomson S, Kumar B, Burr M, Selinger C, Harvey K, Chan C, Beith J, Clouston D, O'Toole SA, Fox SB; kConFab.
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    • The Role of Exosomes in Breast Cancer Diagnosis.
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    • Candidate Markers of Olaparib Response from Genomic Data Analyses of Human Cancer Cell Lines.
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    • Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors.
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    • Nat Commun. 2021 Mar 9;12(1):1502. doi: 10.1038/s41467-021-21783-3.

    Research news:

    Early effects of BRCA1 mutations in the breast.

    • Replication Gaps Underlie BRCA Deficiency and Therapy Response.
    • Panzarino NJ, Krais JJ, Cong K, Peng M, Mosqueda M, Nayak SU, Bond SM, Calvo JA, Doshi MB, Bere M, Ou J, Deng B, Zhu LJ, Johnson N, Cantor SB.
    • Cancer Res. 2021 Mar 1;81(5):1388-1397. doi: 10.1158/0008-5472.CAN-20-1602. Epub 2020 Nov 12.

    Commentary:

    Which Holds the Key to BRCAness: Inability to Repair the Break, Protect the Fork, or Prevent the Gap?

    • [Involvement of Variants in the Genes Encoding BRCA1-Associated Genome Surveillance Complex (BASC) in the Development of Human Common Diseases].
    • Babushkina NP, Postrigan AE, Kucher AN.
    • Mol Biol (Mosk). 2021 Mar-Apr;55(2):318-337. Russian. doi: 10.31857/S0026898421020038.
    • Review, [Article in Russian]
    • LRRK2 inhibition potentiates PARP inhibitor cytotoxicity through inhibiting homologous recombination-mediated DNA double strand break repair.
    • Chen L, Hou J, Zeng X, Guo Q, Deng M, Kloeber JA, Tu X, Zhao F, Wu Z, Huang J, Luo K, Kim W, Lou Z.
    • Clin Transl Med. 2021 Mar;11(3):e341. doi: 10.1002/ctm2.341.
    • Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor.
    • Song D, He H, Sinha I, Hases L, Yan F, Archer A, Haldosen LA, Zhao C, Williams C.
    • Cancer Lett. 2021 Feb 27:S0304-3835(21)00092-6. doi: 10.1016/j.canlet.2021.02.018. Epub ahead of print.
    • BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression.
    • Li Y, Wang Y, Zhang W, Wang X, Chen L, Wang S.
    • Sci Rep. 2021 Feb 26;11(1):4774. doi: 10.1038/s41598-021-82990-y.
    • FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo.
    • Brückner L, Reinshagen A, Hoang NA, Höhn AK, Lordick F, Bechmann I, Aktas B, Nel I, Kallendrusch S.
    • Cancers (Basel). 2021 Feb 25;13(5):956. doi: 10.3390/cancers13050956.
    • The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors.
    • Wu Z, Cui P, Tao H, Zhang S, Ma J, Liu Z, Wang J, Qian Y, Chen S, Huang Z, Zheng X, Huang D, Hu Y.
    • Clin Med Insights Oncol. 2021 Feb 25;15:1179554921996288. doi: 10.1177/1179554921996288.
    • Single-Strand Annealing in Cancer.
    • Blasiak J.
    • Int J Mol Sci. 2021 Feb 22;22(4):2167. doi: 10.3390/ijms22042167.
    • Patient-derived xenograft models of BRCA-associated pancreatic cancers.
    • Golan T, Atias D, Stossel C, Raitses-Gurevich M.
    • Adv Drug Deliv Rev. 2021 Feb 19:S0169-409X(21)00044-2. doi: 10.1016/j.addr.2021.02.010. Epub ahead of print.
    • Review
    • Estrogen enhances the cytotoxicity of PARP inhibitors on breast cancer cells through stimulating nitric oxide production.
    • Zhou S, Liu Y, Jin L, Guo P, Liu Q, Shan J, Luo X, He H, Ma W, Zhang T.
    • J Steroid Biochem Mol Biol. 2021 Feb 19:105853. doi: 10.1016/j.jsbmb.2021.105853. Epub ahead of print.
    • Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer.
    • Chen MK.
    • FEBS J. 2021 Feb 11. doi: 10.1111/febs.15730. Epub ahead of print.
    • Commentary
    • Generation and characterization of induced pluripotent stem cells from a family carrying the BRCA1 mutation c.3612delA.
    • Silva TP, Pereira CA, Oliveira AR, Raposo AC, Arez M, Cabral JMS, Milagre I, Carmo-Fonseca M, da Rocha ST.
    • Stem Cell Res. 2021 Feb 11;52:102242. doi: 10.1016/j.scr.2021.102242. Epub ahead of print.
    • RNF168 regulates R-loop resolution and genomic stability in BRCA1/2-deficient tumors.
    • Patel PS, Abraham KJ, Guturi KKN, Halaby MJ, Khan Z, Palomero L, Ho B, Duan S, St-Germain J, Algouneh A, Mateo F, El Ghamrasni S, Barbour H, Barnes DR, Beesley J, Sanchez O, Berman HK, Brown GW, Affar EB, Chenevix-Trench G, Antoniou AC, Arrowsmith CH, Raught B, Pujana MA, Mekhail K, Hakem A, Hakem R.
    • J Clin Invest. 2021 Feb 1;131(3):e140105. doi: 10.1172/JCI140105.
    • Insufficient evidence of endocervical origin in germline BRCA1 and MSH2-associated tumors.
    • Kertowidjojo E, Park KJ, Hodgson A.
    • Tumori. 2021 Feb 1:300891621991674. doi: 10.1177/0300891621991674. Epub ahead of print.
    • Letter
    • Preclinical evaluation of radiation therapy of BRCA1-associated mammary tumors using a mouse model.
    • Cho EJ, Kim JK, Baek HJ, Kim SE, Park EJ, Choi BK, Kim TH, Shin DH, Lim YK, Deng CX, Kim SS.
    • Int J Biol Sci. 2021 Jan 31;17(3):689-701. doi: 10.7150/ijbs.53667.
    • Radiosensitizing Pancreatic Cancer with PARP Inhibitor and Gemcitabine: An In Vivo and a Whole-Transcriptome Analysis after Proton or Photon Irradiation.
    • Waissi W, Nicol A, Jung M, Rousseau M, Jarnet D, Noel G, Burckel H.
    • Cancers (Basel). 2021 Jan 30;13(3):E527. doi: 10.3390/cancers13030527.
    • Heterogeneity and clonal evolution of acquired PARP inhibitor resistance in TP53- and BRCA1-deficient cells.
    • Färkkilä A, Rodríguez A, Oikkonen J, Gulhan DC, Nguyen H, Domínguez J, Ramos S, Mills CE, Perez-Villatoro F, Lazaro JB, Zhou J, Clairmont CS, Moreau LA, Park PJ, Sorger PK, Hautaniemi S, Frias S, D'Andrea AD.
    • Cancer Res. 2021 Jan 29:canres.2912.2020. doi: 10.1158/0008-5472.CAN-20-2912. Epub ahead of print.
    • DNA replication stress and emerging prospects for PARG inhibitors in ovarian cancer therapy.
    • Pillay N, Brady R, Dey M, Morgan RD, Taylor SS.
    • Prog Biophys Mol Biol. 2021 Jan 29:S0079-6107(21)00005-5. doi: 10.1016/j.pbiomolbio.2021.01.004. Epub ahead of print.
    • Review
    • iPSC-Derived Hereditary Breast Cancer Model Reveals the BRCA1-Deleted Tumor Niche as a New Culprit in Disease Progression.
    • Portier L, Desterke C, Chaker D, Oudrhiri N, Asgarova A, Dkhissi F, Turhan AG, Bennaceur-Griscelli A, Griscelli F.
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    • RUNX3 Transcript Variants Have Distinct Roles in Ovarian Carcinoma and Differently Influence Platinum Sensitivity and Angiogenesis.
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    • Sustained, local delivery of the PARP inhibitor talazoparib prevents the development of mammary gland hyperplasia in Brca1-deficient mice.
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    • Review
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    • Dafni U, Martín-Lluesma S, Balint K, Tsourti Z, Vervita K, Chenal J, Coukos G, Zaman K, Sarivalasis A, Kandalaft LE.
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    • Review
    • Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression.
    • Natoli M, Gallon J, Lu H, Amgheib A, Pinato DJ, Mauri FA, Marafioti T, Akarca AU, Ullmo I, Ip J, Aboagye EO, Brown R, Karadimitris A, Ghaem-Maghami S.
    • J Immunother Cancer. 2021 Jan;9(1):e001519. doi: 10.1136/jitc-2020-001519.
    • Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer.
    • Mehta AK, Cheney EM, Hartl CA, Pantelidou C, Oliwa M, Castrillon JA, Lin JR, Hurst KE, de Oliveira Taveira M, Johnson NT, Oldham WM, Kalocsay M, Berberich MJ, Boswell SA, Kothari A, Johnson S, Dillon DA, Lipschitz M, Rodig S, Santagata S, Garber JE, Tung N, Yélamos J, Thaxton JE, Mittendorf EA, Sorger PK, Shapiro GI, Guerriero JL.
    • Nat Cancer. 2021 Jan;2(1):66-82. doi: 10.1038/s43018-020-00148-7. Epub 2020 Dec 14.

    Research news: PARP Inhibitor Breast Cancer Treatments May Be Improved by Targeting Immunosuppressive Macrophages (Clinical OMICs)

    • Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1.
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    • J Biol Chem. 2020 Dec 24:jbc.RA120.016573. doi: 10.1074/jbc.RA120.016573. Epub ahead of print.
    • The BRCA2 p.N372 H i.a.1342A>C Could Regulate the Sensitivity of Ovarian Cancer Cells to Platinum-Based Drugs.
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    • CRISPR-Cas12a-Based Nucleic Acid Amplification-Free DNA Biosensor via Au Nanoparticle-Assisted Metal-Enhanced Fluorescence and Colorimetric Analysis.
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    • XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib.
    • Ali R, Alblihy A, Toss MS, Algethami M, Al Sunni R, Green AR, Rakha EA, Madhusudan S.
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    • MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/ß-catenin in serous ovarian cancers.
    • Sun Y, Wu J, Dong X, Zhang J, Meng C, Liu G.
    • Transl Oncol. 2020 Dec 21;14(2):100987. doi: 10.1016/j.tranon.2020.100987. Epub ahead of print.
    • PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality-An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness.
    • Gralewska P, Gajek A, Marczak A, Mikula M, Ostrowski J, Sliwinska A, Rogalska A.
    • Int J Mol Sci. 2020 Dec 19;21(24):E9715. doi: 10.3390/ijms21249715.
    • PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response.
    • Riad A, Gitto SB, Lee H, Winters HD, Martorano PM, Hsieh CJ, Xu K, Omran DK, Powell DJ Jr, Mach RH, Makvandi M.
    • Molecules. 2020 Dec 19;25(24):E6029. doi: 10.3390/molecules25246029.
    • Attenuation of SRC kinase activity augments PARP inhibitor-mediated synthetic lethality in BRCA2-altered prostate tumors.
    • Chakraborty G, Khan Patail N, Hirani R, Nandakumar S, Mazzu YZ, Yoshikawa Y, Atiq MO, Jehane L, Stopsack KH, Lee GM, Abida W, Morris MJ, Mucci LA, Danila DC, Kantoff PW.
    • Clin Cancer Res. 2020 Dec 17:clincanres.2483.2020. doi: 10.1158/1078-0432.CCR-20-2483. Epub ahead of print.
    • Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib Via Regulation of Rad-51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells.
    • Cho HY, Kim YB, Park WH, No JH.
    • Cancer Res Treat. 2020 Dec 16. doi: 10.4143/crt.2020.1013. Epub ahead of print.
    • Discovery of isoquinolinone and naphthyridinone-based inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) as anticancer agents: Structure activity relationship and preclinical characterization.
    • Karche NP, Bhonde M, Sinha N, Jana G, Kukreja G, Kurhade SP, Jagdale AR, Tilekar AR, Hajare AK, Jadhav GR, Gupta NR, Limaye R, Khedkar N, Thube BR, Shaikh JS, Rao Irlapati N, Phukan S, Gole G, Bommakanti A, Khanwalkar H, Pawar Y, Kale R, Kumar R, Gupta R, Praveen Kumar VR, Wahid S, Francis A, Bhat T, Kamble N, Patil V, Nigade PB, Modi D, Pawar S, Naidu S, Volam H, Pagdala V, Mallurwar S, Goyal H, Bora P, Ahirrao P, Singh M, Kamalakannan P, Naik KR, Kumar P, Powar RG, Shankar RB, Bernstein PR, Gundu J, Nemmani K, Narasimham L, George KS, Sharma S, Bakhle D, Kamboj RK, Palle VP.
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    • A very long-acting Poly(ADP-ribose) polymerase inhibitor suppresses cancer cell growth in DNA repair-deficient tumor models.
    • Fontaine SD, Ashley GW, Houghton PJ, Kurmasheva RT, Diolaiti M, Ashworth A, Peer CJ, Nguyen R, Figg WD, Beckford-Vera DR, Santi DV.
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    • Differential immunomodulatory Effect of PARP Inhibition in BRCA1 deficient and competent tumor cells.
    • Alvarado-Cruz I, Mahmoud M, Khan M, Zhao S, Oeck S, Meas R, Clairmont K, Quintana V, Zhu Y, Porciuncula A, Wyatt H, Ma S, Shyr Y, Kong Y, LoRusso PM, Laverty D, Nagel ZD, Schalper KA, Krauthammer M, Sweasy JB.
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    • Dextran-modified Quercetin-Cu(II)/hyaluronic acid nanomedicine with natural poly(ADP-ribose) polymerase inhibitor and dual targeting for programmed synthetic lethal therapy in triple-negative breast cancer.
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    • J Control Release. 2020 Dec 2:S0168-3659(20)30718-5. doi: 10.1016/j.jconrel.2020.11.061. Epub ahead of print.
    • Combinatorial efficacy of olaparib with radiation and ATR inhibitor requires PARP1 protein in homologous recombination proficient pancreatic cancer.
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    • Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis?
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    • The effect of the triazene compound CT913 on ovarian cancer cells in vitro and its synergistic interaction with the PARP-inhibitor olaparib.
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    • Inhibition of poly(ADP-ribose) polymerase induces synthetic lethality in BRIP1 deficient ovarian epithelial cells.
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    • Homologous recombination deficiency real-time clinical assays, ready or not?
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    • Review
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    • Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial.
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    • Novel poly (ADP-ribose) polymerases inhibitor DHC-1 exhibits in vitro and in vivo anticancer activity on BRCA-deficient pancreatic cancer cells.
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    • ANKLE-1 as new hotspot mutation for Breast cancer in Indian population and has a role in DNA Damage and repair in mammalian cells.
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    • Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens.
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    • A Review of Natural Therapies Potentially Relevant in Triple Negative Breast Cancer Aimed at Targeting Cancer Cell Vulnerabilities.
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    • Identification of 2-substituted pyrrolo[1,2-b]pyridazine derivatives as new PARP-1 inhibitors.
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    • Bioorg Med Chem Lett. 2020 Nov 24:127710. doi: 10.1016/j.bmcl.2020.127710. Epub ahead of print.
    • Dual Modulators of p53 and Cyclin D in ER Alpha Signaling by Albumin Nanovectors Bearing Zinc Chaperones for ER Positive Breast Cancer Therapy.
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    • Commentary
    • Classification of ovarian cancer associated with BRCA1 mutations, immune checkpoints, and tumor microenvironment based on immunogenomic profiling.
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    • Glucose Concentration in Cell Culture Medium Influences the BRCA1-Mediated Regulation of the Lipogenic Action of IGF-I in Breast Cancer Cells.
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    • The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer.
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    • Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers.
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    • Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants.
    • Iqbal S, Pérez-Palma E, Jespersen JB, May P, Hoksza D, Heyne HO, Ahmed SS, Rifat ZT, Rahman MS, Lage K, Palotie A, Cottrell JR, Wagner FF, Daly MJ, Campbell AJ, Lal D.
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    • PARP Inhibitor Olaparib Causes No Potentiation of the Bleomycin Effect in VERO Cells, Even in the Presence of Pooled ATM, DNA-PK, and LigIV Inhibitors.
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    • Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1.
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    • Suppression of DDX39B sensitizes ovarian cancer cells to DNA-damaging chemotherapeutic agents via destabilizing BRCA1 mRNA.
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    • RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational Status.
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    • Regulation of breast cancer oncogenesis by the cell of origin's differentiation state.
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    • Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3.
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    • BARD1 and Breast Cancer: The Possibility of Creating Screening Tests and New Preventive and Therapeutic Pathways for Predisposed Women.
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    • Ideaya Biosciences, Broad Institute Partner on Synthetic Lethality-Based Cancer Drug Discovery.
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    • Exploring role of 5hmC as potential marker of chemoresistance.
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    • Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium.
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    • BMC Cancer. 2020 Oct 21;20(1):1020. doi: 10.1186/s12885-020-07524-7.
    • Lessons learned from setting up a prospective, longitudinal, multicenter study with women at high risk for breast cancer.
    • Patuleia SIS, Hagenaars SC, Moelans CB, Ausems MGEM, van Gils CH, Tollenaar RAEM, Van Diest PJ, Mesker WE, van der Wall E.
    • Cancer Epidemiol Biomarkers Prev. 2020 Oct 20:cebp.0770.2020. doi: 10.1158/1055-9965.EPI-20-0770. Epub ahead of print.
    • Review
    • Repurposing denosumab in breast cancer beyond prevention of skeletal related events: could nonclinical data be translated into clinical practice?
    • Deligiorgi MV, Panayiotidis MI, Trafalis DT.
    • Expert Rev Clin Pharmacol. 2020 Oct 17. doi: 10.1080/17512433.2020.1839416. Epub ahead of print.
    • Review
    • Ultrasensitive colorimetric biosensor for BRCA1 mutation based on multiple signal amplification strategy.
    • Bai Y, Li H, Xu J, Huang Y, Zhang X, Weng J, Li Z, Sun L.
    • Biosens Bioelectron. 2020 Oct 15;166:112424. doi: 10.1016/j.bios.2020.112424. Epub 2020 Jul 11.
    • The abundance of the long intergenic non-coding RNA 01087 differentiates between luminal and triple-negative breast cancers and predicts patient outcome.
    • De Palma FDE, Monaco VD, Pol JG, Kremer M, D'Argenio V, Stoll G, Montanaro D, Uszczynska-Ratajczak B, Klein CC, Vlasova A, Botti G, D'Aiuto M, Baldi A, Guigó R, Kroemer G, Maiuri MC, Salvatore F.
    • Pharmacol Res. 2020 Oct 14:105249. doi: 10.1016/j.phrs.2020.105249. Epub ahead of print.
    • Targeting SMYD3 to Sensitize Homologous Recombination-Proficient Tumors to PARP-Mediated Synthetic Lethality.
    • Sanese P, Fasano C, Buscemi G, Bottino C, Corbetta S, Fabini E, Silvestri V, Valentini V, Disciglio V, Forte G, Lepore Signorile M, De Marco K, Bertora S, Grossi V, Guven U, Porta N, Di Maio V, Manoni E, Giannelli G, Bartolini M, Del Rio A, Caretti G, Ottini L, Simone C.
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    • Prioritizing disease biomarkers using functional module based network analysis: A multilayer consensus driven scheme.
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    • Ablation of the Brca1-Palb2 Interaction Phenocopies Fanconi Anemia in Mice.
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    Comment, Research review:

    BRCA1 and PALB2 in a Messy Breakup.

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    Commentary:

    A Novel Mechanism to Induce BRCAness in Cancer Cells.

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    Commentary:

    Not Black or White but Shades of Gray: Homologous Recombination Deficiency as a Continuous Variable Modulated by RNF168.

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    • miRNA expression profiling of hereditary breast tumors from BRCA1- and BRCA2-germline mutation carriers in Brazil.
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    • Olaparib Combined with an ATR or Chk1 Inhibitor as a Treatment Strategy for Acquired Olaparib-Resistant BRCA1 Mutant Ovarian Cells.
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    • Association of BRCA Mutantations and BRCAness Status With Anticancer Drug Sensitivities in Triple-Negative Breast Cancer Cell Lines.
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    • Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups.
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    • Association Between Genetically Proxied Inhibition of HMG-CoA Reductase and Epithelial Ovarian Cancer.
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    • BRCA1 Deficiency Impairs Mitophagy and Promotes Inflammasome Activation and Mammary Tumor Metastasis.
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    • BTH-8, a novel poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, causes DNA double-strand breaks and exhibits anticancer activities in vitro and in vivo.
    • Guo C, Zhang F, Wu X, Yu X, Wu X, Shi D, Wang L.
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    • PALB2 chromatin recruitment restores homologous recombination in BRCA1-deficient cells depleted of 53BP1.
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    • TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy.
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    • Blocking c-Met and EGFR reverses acquired resistance of PARP inhibitors in triple-negative breast cancer.
    • Chu YY, Yam C, Chen MK, Chan LC, Xiao M, Wei YK, Yamaguchi H, Lee PC, Han Y, Nie L, Sun X, Moulder SL, Hess KR, Wang B, Hsu JL, Hortobagyi GN, Litton J, Chang JT, Hung MC.
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    • Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer.
    • Xiao G, Lundine D, Annor GK, Canar J, Ellison V, Polotskaia A, Donabedian PL, Reiner T, Khramtsova GF, Olopade OI, Mazo A, Bargonetti J.
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    Press: Triple negative breast cancer might not actually be ‘breast cancer’. (Clinical OMICs)

    • Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets.
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    • Design, Synthesis, and In Vitro Evaluation of the Photoactivatable Prodrug of the PARP Inhibitor Talazoparib.
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    • Molecules. 2020 Jan 18;25(2). pii: E407. doi: 10.3390/molecules25020407.
    • Divergent metabolic responses dictate vulnerability to NAMPT-inhibition in ovarian cancer.
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    • Declining BRCA-Mediated DNA Repair in Sperm Aging and its Prevention by Sphingosine-1-Phosphate.
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    • The metallo-intercalator [Ru(dppz)2(PIP)]2+ renders BRCA wild-type triple-negative breast cancer cells hypersensitive to PARP inhibition.
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    • CRISPR/Cas9-mediated mutagenesis to validate the synergy between PARP1 inhibition and chemotherapy in BRCA1-mutated breast cancer cells.
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    • Bioeng Transl Med. 2020 Jan 2;5(1):e10152. doi: 10.1002/btm2.10152. eCollection 2020 Jan.
    • MiR-200c sensitizes Olaparib-resistant ovarian cancer cells by targeting Neuropilin 1.
    • Vescarelli E, Gerini G, Megiorni F, Anastasiadou E, Pontecorvi P, Solito L, De Vitis C, Camero S, Marchetti C, Mancini R, Benedetti Panici P, Dominici C, Romano F, Angeloni A, Marchese C, Ceccarelli S.
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    • Color Data v2: a user-friendly, open-access database with hereditary cancer and hereditary cardiovascular conditions datasets.
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    • A new class of coumate benzimidazole hybrids as BRCA-1 mimetics through unconventional binding mode; Synthesis and preliminary cytotoxicity screening.
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    • Low-Dose and Long-Term Olaparib Treatment Sensitizes MDA-MB-231 and SUM1315 Triple-Negative Breast Cancers Spheroids to Fractioned Radiotherapy.
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    • Colocalization of BRCA1 with Tau Aggregates in Human Tauopathies.
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    • Discovery of Novel Dual Poly(ADP-ribose)polymerase (PARP) and Phosphoinositide 3-kinase (PI3K) Inhibitors as A Promising Strategy for Cancer Therapy.
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    • Interferon-γ signaling is associated with BRCA1 loss-of-function mutations in high grade serous ovarian cancer.
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    • Genistein Inhibits Proliferation of BRCA1 Mutated Breast Cancer Cells: The GPR30-Akt Axis as a Potential Target.
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    • Poly(adenosine diphosphate ribose) polymerase inhibitors induce autophagy-mediated drug resistance in ovarian cancer cells, xenografts, and patient-derived xenograft models.
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    • The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.
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    • NPJ Breast Cancer. 2019 Nov 1;5:38. doi: 10.1038/s41523-019-0127-5. eCollection 2019.
    • Differences in cysteine peptidases-like activity in sera of patients with breast cancer.
    • Kilar E, Siewiński M, Hirnle L, Skiba T, Goła B K, Gburek J, Murawski M, Janocha A.
    • Cancer Biomark. 2019 Oct 25. doi: 10.3233/CBM-190327. [Epub ahead of print]
    • PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells.
    • Quinet A, Tirman S, Jackson J, Šviković S, Lemaçon D, Carvajal-Maldonado D, González-Acosta D, Vessoni AT, Cybulla E, Wood M, Tavis S, Batista LFZ, Méndez J, Sale JE, Vindigni A.
    • Mol Cell. 2019 Oct 23. pii: S1097-2765(19)30768-3. doi: 10.1016/j.molcel.2019.10.008. [Epub ahead of print]

    Research news:

    The PRIMPOL Protein Shields Replication Forks in BRCA-Deficient Cells.

    • RAD6B is a major mediator of triple negative breast cancer cisplatin resistance: Regulation of translesion synthesis/Fanconi anemia crosstalk and BRCA1 independence.
    • Haynes B, Gajan A, Nangia-Makker P, Shekhar MP.
    • Biochim Biophys Acta Mol Basis Dis. 2019 Oct 19:165561. doi: 10.1016/j.bbadis.2019.165561. [Epub ahead of print]
    • BRCA1 Deficiency Upregulates NNMT Which Reprograms Metabolism and Sensitizes Ovarian Cancer Cells to Mitochondrial Metabolic Targeting Agents.
    • Kanakkanthara A, Kurmi K, Ekstrom TL, Hou X, Purfeerst ER, Heinzen EP, Correia C, Huntoon CJ, O'Brien D, Wahner Hendrickson AE, Dowdy SC, Li H, Oberg AL, Hitosugi T, Kaufmann SH, Weroha SJ, Karnitz LM.
    • Cancer Res. 2019 Oct 16. pii: canres.1405.2019. doi: 10.1158/0008-5472.CAN-19-1405. [Epub ahead of print]
    • A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors.
    • Gerdur Ísberg Ó, Kim J, Fridriksdottir AJ, Morsing M, Timmermans-Wielenga V, Rønnov-Jessen L, Petersen OW, Villadsen R.
    • Sci Rep. 2019 Oct 16;9(1):14843. doi: 10.1038/s41598-019-50903-9.
    • Exploring the Clinical Impact of Predictive Biomarkers in Serous Ovarian Carcinomas.
    • Page CL, Chung J, Rahimi K, Kobel M, Provencher D, Masson AMM.
    • Curr Drug Targets. 2019 Oct 16. doi: 10.2174/1389450120666191016143836. [Epub ahead of print]
    • Review
    • WIP1 Promotes Homologous Recombination and Modulates Sensitivity to PARP Inhibitors.
    • Burdova K, Storchova R, Palek M, Macurek L
    • Cells. 2019 Oct 15;8(10). pii: E1258. doi: 10.3390/cells8101258.
    • Synergistic Effect of a HER2 Targeted Thorium-227 Conjugate in Combination with Olaparib in a BRCA2 Deficient Xenograft Model.
    • Wickstroem K, Karlsson J, Ellingsen C, Cruciani V, Kristian A, Hagemann UB, Bjerke RM, Ryan OB, Linden L, Mumberg D, Brands M, Cuthbertson A.
    • Pharmaceuticals (Basel). 2019 Oct 15;12(4). pii: E155. doi: 10.3390/ph12040155.
    • RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies.
    • Toma M, Sullivan-Reed K, Śliwiński T, Skorski T.
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    Research news:

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    • Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation the Therapeutic Efficacy In Vitro.
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    • DAXX, as a Tumor Suppressor, Impacts DNA Damage Repair and Sensitizes BRCA-Proficient TNBC Cells to PARP Inhibitors.
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    • Dual TGFβ/BMP pathway inhibition enables expansion and characterization of multiple epithelial cell types of the normal and cancerous breast.
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    • N6-methylation of adenosine (m6A) of FZD10 mRNA contributes to PARP inhibitor resistance.
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    • Rapid activation of epithelial-mesenchymal transition drives PARP inhibitor resistance in Brca2-mutant mammary tumours.
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    • Dissecting PARP inhibitor resistance with functional genomics.
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    • 4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion.
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    Commentary:

    Fighting against the challenge of treating patients with late-line ovarian cancer: are we there yet?

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    • GnRH-R targeted lytic peptide sensitizes BRCA wild-type ovarian cancer to PARP inhibition.
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    • Review
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    • Integrating Germline and Somatic Mutation Information for the Discovery of Biomarkers in Triple-Negative Breast Cancer.
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    • BRCA1 Haploinsufficiency Is Masked by RNF168-Mediated Chromatin Ubiquitylation.
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    Research news:

    Context Matters: RNF168 Connects with PALB2 to Rewire Homologous Recombination in BRCA1 Haploinsufficiency.

    • Polo-like Kinase 1 inhibition as a therapeutic approach to selectively target BRCA1-deficient cancer cells by synthetic lethality induction.
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    • DNA Replication Vulnerabilities Render Ovarian Cancer Cells Sensitive to Poly(ADP-Ribose) Glycohydrolase Inhibitors.
    • Pillay N, Tighe A, Nelson L, Littler S, Coulson-Gilmer C, Bah N, Golder A, Bakker B, Spierings DCJ, James DI, Smith KM, Jordan AM, Morgan RD, Ogilvie DJ, Foijer F, Jackson DA, Taylor SS.
    • Cancer Cell. 2019 Mar 18;35(3):519-533.e8. doi: 10.1016/j.ccell.2019.02.004.
    • DNA polymerase θ (POLQ) is important for repair of DNA double-strand breaks caused by fork collapse.
    • Wang Z, Song Y, Li S, Kurian S, Xiang R, Chiba T, Wu X.
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    • The deubiquitylating enzyme USP15 regulates homologous recombination repair and cancer cell response to PARP inhibitors.
    • Peng Y, Liao Q, Tan W, Peng C, Hu Z, Chen Y, Li Z, Li J, Zhen B, Zhu W, Li X, Yao Y, Song Q, Liu C, Qi X, He F, Pei H.
    • Nat Commun. 2019 Mar 15;10(1):1224. doi: 10.1038/s41467-019-09232-8.

    Press: New Biomarker Could Expand Effective PARP Inhibitor Treatment Options. (Clinical OMICs)

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    • Exploring the Frequency of Homologous Recombination DNA Repair Dysfunction in Multiple Cancer Types.
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    • Beyond DNA repair: the novel immunological potential of PARP inhibitors.
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    • Mol Cell Oncol. 2019 Mar 13;6(2):1585170. doi: 10.1080/23723556.2019.1585170. eCollection 2019.
    • Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS.
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    • Molecules. 2019 Mar 11;24(5). pii: E989. doi: 10.3390/molecules24050989.
    • Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets.
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    • Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells.
    • Han Y, Chen MK, Wang HL, Hsu JL, Li CW, Chu YY, Liu CX, Nie L, Chan LC, Yam C, Wang SC, He GJ, Hortobagyi GN, Tan XD, Hung MC.
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    • Rad51/BRCA2 disruptors inhibit homologous recombination and synergize with olaparib in pancreatic cancer cells.
    • Roberti M, Schipani F, Bagnolini G, Milano D, Giacomini E, Falchi F, Balboni A, Manerba M, Farabegoli F, De Franco F, Robertson J, Minucci S, Pallavicini I, Di Stefano G, Girotto S, Pellicciari R, Cavalli A.
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    • BRCA1 represses DNA replication initiation through antagonizing estrogen signaling and maintains genome stability in parallel with WEE1-MCM2 signaling during pregnancy.
    • Xu X, Chen E, Mo L, Zhang L, Shao F, Miao K, Liu J, Su SM, Valecha M, In Chan U, Zheng H, Chen M, Chen W, Chen Q, Fu H, Aladjem MI, He Y, Deng CX.
    • Hum Mol Genet. 2019 Mar 1;28(5):842-857. doi: 10.1093/hmg/ddy398.
    • The Fanconi Anemia Pathway in Cancer.
    • Niraj J, Färkkilä A, D'Andrea AD.
    • Annu Rev Cancer Biol. 2019 Mar;3:457-478. doi: 10.1146/annurev-cancerbio-030617-050422. Epub 2018 Dec 3.
    • Pharmacologic characterization of fluzoparib, a novel poly(ADP-ribose) polymerase inhibitor undergoing clinical trials.
    • Wang L, Yang C, Xie C, Jiang J, Gao M, Fu L, Li Y, Bao X, Fu H, Lou L.
    • Cancer Sci. 2019 Mar;110(3):1064-1075. doi: 10.1111/cas.13947. Epub 2019 Feb 19.
    • Modeling malignancies using induced pluripotent stem cells: from chronic myeloid leukemia to hereditary cancers.
    • Turhan A, Foudi A, Hwang JW, Desterke C, Griscelli F, Bennaceur-Griscelli A.
    • Exp Hematol. 2019 Mar;71:61-67. doi: 10.1016/j.exphem.2019.01.003. Epub 2019 Jan 16.
    • E-cadherin-deficient cells have synthetic lethal vulnerabilities in plasma membrane organisation, dynamics and function.
    • Godwin TD, Kelly ST, Brew TP, Bougen-Zhukov NM, Single AB, Chen A, Stylianou CE, Harris LD, Currie SK, Telford BJ, Beetham HG, Evans GB, Black MA, Guilford PJ.
    • Gastric Cancer. 2019 Mar;22(2):273-286. doi: 10.1007/s10120-018-0859-1. Epub 2018 Jul 31.
    • Targeting the lysosome by an aminomethylated Riccardin D triggers DNA damage through cathepsin B-mediated degradation of BRCA1.
    • Wang Y, Niu H, Hu Z, Zhu M, Wang L, Han L, Qian L, Tian K, Yuan H, Lou H.
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    • CRISPR/Cas9-Mediated BRCA1 Knockdown Adipose Stem Cells Promote Breast Cancer Progression.
    • Zhao R, Kaakati R, Liu X, Xu L, Lee AK, Bachelder R, Li CY, Hollenbeck ST.
    • Plast Reconstr Surg. 2019 Mar;143(3):747-756. doi: 10.1097/PRS.0000000000005316.

    Research news:

    Discussion: CRISPR/Cas9-Mediated BRCA1 Knockdown Adipose Stem Cells Promote Breast Cancer Progression.

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    • Tumor suppressor MCPH1 regulates gene expression profiles related to malignant conversion and chromosomal assembly.
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    • Genetic variation and radiation quality impact cancer promoting cellular phenotypes in response to HZE exposure.
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    • Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models.
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    • Evaluation of site-specific homologous recombination activity of BRCA1 by direct quantitation of gene editing efficiency.
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    • Quantifying BRCA1 and BRCA2 mRNA Isoform Expression Levels in Single Cells.
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    • Radiosensitivity Is an Acquired Vulnerability of PARPi-Resistant BRCA1-Deficient Tumors.
    • Barazas M, Gasparini A, Huang Y, Küçükosmanoğlu A, Annunziato S, Bouwman P, Sol W, Kersbergen A, Proost N, de Korte-Grimmerink R, van de Ven M, Jonkers J, Borst GR, Rottenberg S.
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    • Mifepristone mediates anti-proliferative effect on ovarian mesenchymal stem/stromal cells from female BRCA1-/2- carriers.
    • Ponandai-Srinivasan S, Lalitkumar PG, Garcia L, Varghese SJ, Carlson JW, Gemzell-Danielsson K, Floter Radestad A.
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    • Exaggeration of PFS by blinded, independent, central review (BICR).
    • Stone A, Gebski V, Davidson R, Bloomfield R, Bartlett JW, Sabin A.
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    • A mouse model featuring tissue-specific deletion of p53 and Brca1 gives rise to mammary tumors with genomic and transcriptomic similarities to human basal-like breast cancer.
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    • The fallopian tube, "precursor escape" and narrowing the knowledge gap to the origins of high-grade serous carcinoma.
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    • Review
    • Induced in vivo knockdown of the Brca1 gene in skeletal muscle results in skeletal muscle weakness.
    • Tarpey MD, Valencia AP, Jackson KC, Amorese AJ, Balestrieri NP, Renegar RH, Pratt SJP, Ryan TE, McClung JM1,, Lovering RM, Spangenburg EE.
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    • PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow.
    • Hopkins TA, Ainsworth WB, Ellis PA, Donawho CK, DiGiammarino EL, Panchal SC, Abraham VC, Algire MA, Shi Y, Olson AM, Johnson EF, Wilsbacher JL, Maag D.
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    • PARP Inhibition Induces Enrichment of DNA Repair-Proficient CD133 and CD117 Positive Ovarian Cancer Stem Cells.
    • Bellio C, DiGloria C, Foster R, James K, Konstantinopoulos PA, Growdon WB, Rueda BR.
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    • CHK2-mediated regulation of PARP1 in oxidative DNA damage response.
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    • Oncogene. 2019 Feb;38(8):1166-1182. doi: 10.1038/s41388-018-0506-7. Epub 2018 Sep 25.
    • Treating metastatic breast cancer: Analysis of the impact of palbociclib (Ibrance) on overall survival in the PALOMA-3 trial.
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    • Annunziato S, de Ruiter JR, Henneman L, Brambillasca CS, Lutz C, Vaillant F, Ferrante F, Drenth AP, van der Burg E, Siteur B, van Gerwen B, de Bruijn R, van Miltenburg MH, Huijbers IJ, van de Ven M, Visvader JE, Lindeman GJ, Wessels LFA, Jonkers J.
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    • BRCA1 and Breast Cancer: a Review of the Underlying Mechanisms Resulting in the Tissue-Specific Tumorigenesis in Mutation Carriers.
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    • The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers.
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    • Sequential therapeutic targeting of ovarian Cancer harboring dysfunctional BRCA1.
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