Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 May 15

PMID 32403357

Citations 5

Authors

Sara Bouberhan

Lauren Philp

Sarah Hill

Linah F Al-Alem

Bo Rueda

Affiliations

Soon will be listed here.

Abstract

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer. In this review, we explore the preclinical and clinical studies that led to the development of FDA approved drugs that take advantage of the synthetic lethality concept, the implementation of the early phase trials, the development of companion diagnostics and proposed mechanisms of resistance.

Citing Articles

Unveiling the novel immune and molecular signatures of ovarian cancer: insights and innovations from single-cell sequencing.

Li Z, Gu H, Xu X, Tian Y, Huang X, Du Y Front Immunol. 2023; 14:1288027.

PMID: 38022625 PMC: 10654630. DOI: 10.3389/fimmu.2023.1288027.

Cellular Functions of Deubiquitinating Enzymes in Ovarian Adenocarcinoma.

Min Y, Park H, Baek K, Hwang S Genes (Basel). 2023; 14(4).

PMID: 37107644 PMC: 10137459. DOI: 10.3390/genes14040886.

Concordance between single-nucleotide polymorphism-based genomic instability assays and a next-generation sequencing-based homologous recombination deficiency test.

Cristescu R, Liu X, Arreaza G, Chen C, Albright A, Qiu P BMC Cancer. 2022; 22(1):1310.

PMID: 36517748 PMC: 9749332. DOI: 10.1186/s12885-022-10197-z.

Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer.

Launonen I, Lyytikainen N, Casado J, Anttila E, Szabo A, Haltia U Nat Commun. 2022; 13(1):835.

PMID: 35149709 PMC: 8837628. DOI: 10.1038/s41467-022-28389-3.

The Chromatin Response to Double-Strand DNA Breaks and Their Repair.

Aleksandrov R, Hristova R, Stoynov S, Gospodinov A Cells. 2020; 9(8).

PMID: 32784607 PMC: 7464352. DOI: 10.3390/cells9081853.

References

Rondinelli B, Gogola E, Yucel H, Duarte A, van de Ven M, van der Sluijs R . EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nat Cell Biol. 2017; 19(11):1371-1378. DOI: 10.1038/ncb3626. View

Eustermann S, Wu W, Langelier M, Yang J, Easton L, Riccio A . Structural Basis of Detection and Signaling of DNA Single-Strand Breaks by Human PARP-1. Mol Cell. 2015; 60(5):742-754. PMC: 4678113. DOI: 10.1016/j.molcel.2015.10.032. View

Frey M, Pothuri B . Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. Gynecol Oncol Res Pract. 2017; 4:4. PMC: 5322589. DOI: 10.1186/s40661-017-0039-8. View

Alsop K, Fereday S, Meldrum C, DeFazio A, Emmanuel C, George J . BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 2012; 30(21):2654-63. PMC: 3413277. DOI: 10.1200/JCO.2011.39.8545. View

Lord C, Ashworth A . The DNA damage response and cancer therapy. Nature. 2012; 481(7381):287-94. DOI: 10.1038/nature10760. View

Wang Y, Bernhardy A, Cruz C, Krais J, Nacson J, Nicolas E . The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin. Cancer Res. 2016; 76(9):2778-90. PMC: 4874568. DOI: 10.1158/0008-5472.CAN-16-0186. View

Gibson B, Kraus W . New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol. 2012; 13(7):411-24. DOI: 10.1038/nrm3376. View

ONeil N, Bailey M, Hieter P . Synthetic lethality and cancer. Nat Rev Genet. 2017; 18(10):613-623. DOI: 10.1038/nrg.2017.47. View

Welcsh P, King M . BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum Mol Genet. 2001; 10(7):705-13. DOI: 10.1093/hmg/10.7.705. View

10.

Vaidyanathan A, Sawers L, Gannon A, Chakravarty P, Scott A, Bray S . ABCB1 (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells. Br J Cancer. 2016; 115(4):431-41. PMC: 4985349. DOI: 10.1038/bjc.2016.203. View

11.

Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G . Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014; 32(13):1302-8. DOI: 10.1200/JCO.2013.51.4489. View

12.

Ray Chaudhuri A, Callen E, Ding X, Gogola E, Duarte A, Lee J . Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature. 2016; 535(7612):382-7. PMC: 4959813. DOI: 10.1038/nature18325. View

13.

Walker J, Brady M, Wenzel L, Fleming G, Huang H, DiSilvestro P . Randomized Trial of Intravenous Versus Intraperitoneal Chemotherapy Plus Bevacizumab in Advanced Ovarian Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol. 2019; 37(16):1380-1390. PMC: 6544459. DOI: 10.1200/JCO.18.01568. View

14.

Morganella S, Alexandrov L, Glodzik D, Zou X, Davies H, Staaf J . The topography of mutational processes in breast cancer genomes. Nat Commun. 2016; 7:11383. PMC: 5001788. DOI: 10.1038/ncomms11383. View

15.

Lord C, Ashworth A . PARP inhibitors: Synthetic lethality in the clinic. Science. 2017; 355(6330):1152-1158. PMC: 6175050. DOI: 10.1126/science.aam7344. View

16.

Coleman R, Oza A, Lorusso D, Aghajanian C, Oaknin A, Dean A . Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017; 390(10106):1949-1961. PMC: 5901715. DOI: 10.1016/S0140-6736(17)32440-6. View

17.

Weigelt B, Comino-Mendez I, de Bruijn I, Tian L, Meisel J, Garcia-Murillas I . Diverse and Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer. Clin Cancer Res. 2017; 23(21):6708-6720. PMC: 5728372. DOI: 10.1158/1078-0432.CCR-17-0544. View

18.

Murai J, Huang S, Das B, Renaud A, Zhang Y, Doroshow J . Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012; 72(21):5588-99. PMC: 3528345. DOI: 10.1158/0008-5472.CAN-12-2753. View

19.

Murai J, Huang S, Renaud A, Zhang Y, Ji J, Takeda S . Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther. 2013; 13(2):433-43. PMC: 3946062. DOI: 10.1158/1535-7163.MCT-13-0803. View

20.

Moore K, Secord A, Geller M, Miller D, Cloven N, Fleming G . Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019; 20(5):636-648. DOI: 10.1016/S1470-2045(19)30029-4. View