Investigational PARP inhibitors for the treatment of biliary tract cancer: spotlight on preclinical and clinical studies

References

• Malenica I, Donadon M, Molecular LA. Immunological characterization of biliary tract cancers: a paradigm shift towards a personalized medicine. Cancers (Basel). 2020 Aug 6;12(8):2190.
   PubMed Web of Science ®Google Scholar
• Bile Duct Cancer (Cholangiocarcinoma). Statistics: ASCO; 2020 [cited 2020 Dec 18]. Available from: https://www.cancer.net/cancer-types/bile-duct-cancer-cholangiocarcinoma/statistics
   Google Scholar
• Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273–1281.
   PubMed Web of Science ®Google Scholar
• Lamarca A, Palmer DH, Wasan HS, et al. ABC-06 | a randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J clin oncol. 2019;37(15_suppl):4003.
   Web of Science ®Google Scholar
• Jain A, Javle M. Molecular profiling of biliary tract cancer: a target rich disease. J Gastrointest Oncol. 2016 Oct;7(5):797–803.
   PubMed Web of Science ®Google Scholar
• Valle JW, Lamarca A, Goyal L, et al. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017 Sep;7(9):943–962.
   PubMed Web of Science ®Google Scholar
• Montal R, Sia D, Montironi C, et al. Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma. J Hepatol. 2020 Aug;73(2):315–327.
   PubMed Web of Science ®Google Scholar
• Personeni N, Lleo A, Pressiani T, et al. Biliary tract cancers: molecular heterogeneity and new treatment options. Cancers (Basel). 2020 13; 12(11): Nov.
   Web of Science ®Google Scholar
• Goyal L, Deshpande V, Chung DC, et al. Mismatch repair protein loss and microsatellite instability in cholangiocarcinoma. J clin oncol. 2014;32(3_suppl):237.
   Web of Science ®Google Scholar
• FDA grants accelerated approval to pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion: FDA; 2020 [cited 2020 Dec 18]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement-or-fusion
   Google Scholar
• Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796–807.
   PubMed Web of Science ®Google Scholar
• Subbiah V, Lassen U, Elez E, et al. Dabrafenib plus trametinib in patients with BRAF(V600E)-mutated
   Google Scholar
• Rizzo A, Frega G, Ricci AD, et al. Anti-EGFR monoclonal antibodies in advanced biliary tract cancer: a systematic review and meta-analysis. Vivo. 2020 Mar-Apr;34(2):479–488.
   PubMed Web of Science ®Google Scholar
• Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523–533.
   PubMed Web of Science ®Google Scholar
• Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317–327.
   PubMed Web of Science ®Google Scholar
• De Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020 May 28;382(22):2091–2102.
   PubMed Web of Science ®Google Scholar
• Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018 Dec 27;379(26):2495–2505.
   PubMed Web of Science ®Google Scholar
• Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019 Dec 19;381(25):2416–2428.
   PubMed Web of Science ®Google Scholar
• Boussios S, Abson C, Moschetta M, et al. Poly (ADP-Ribose) polymerase inhibitors: talazoparib in ovarian cancer and beyond. Drugs R D. 2020 Jun;20(2):55–73.
   PubMed Web of Science ®Google Scholar
• Brown JS, O’Carrigan B, Jackson SP, et al. Targeting DNA repair in cancer: beyond PARP inhibitors. Cancer Discov. 2017 Jan;7(1):20–37.
   PubMed Web of Science ®Google Scholar
• Lord CJ, Ashworth A. BRCAness revisited. Nat Rev Cancer. 2016 Feb;16(2):110–120.
   PubMed Web of Science ®Google Scholar
• Ame JC, Spenlehauer C, De Murcia G. The PARP superfamily. Bioessays. 2004 Aug;26(8):882–893.
   PubMed Web of Science ®Google Scholar
• De Vos M, Schreiber V, Dantzer F. The diverse roles and clinical relevance of PARPs in DNA damage repair: current state of the art. Biochem Pharmacol. 2012 Jul 15;84(2):137–146.
   PubMed Web of Science ®Google Scholar
• Caldecott KW. DNA single-strand break repair. Exp Cell Res. 2014 Nov 15;329(1):2–8.
   PubMed Web of Science ®Google Scholar
• Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012 Nov 1;72(21):5588–5599.
   PubMed Web of Science ®Google Scholar
• Ricci AD, Rizzo A, Bonucci C, et al. PARP inhibitors in biliary tract cancer: a new kid on the block? Medicines (Basel). 2020 Aug 31;7(9):9.
   Google Scholar
• Morales J, Li L, Fattah FJ, et al. Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit Rev Eukaryot Gene Expr. 2014;24(1):15–28.
   PubMed Web of Science ®Google Scholar
• Spizzo G, Puccini A, Xiu J, et al. Molecular profile of BRCA-mutated biliary tract cancers. ESMO Open. 2020 Jun;5(3):e000682.
   Web of Science ®Google Scholar
• Tutt A, Bertwistle D, Valentine J, et al. Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. Embo J. 2001 Sep 3;20(17):4704–4716.
   PubMed Web of Science ®Google Scholar
• Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003 Oct 20;22(47):7265–7279.
   PubMed Web of Science ®Google Scholar
• Knijnenburg TA, Wang L, Zimmermann MT, et al. Genomic and molecular landscape of DNA damage repair deficiency across the cancer genome atlas. Cell Rep. 2018 Apr 3;23(1):239–254 e6.
   PubMed Web of Science ®Google Scholar
• Pellegrino B, Mateo J, Serra V, et al. Controversies in oncology: are genomic tests quantifying homologous recombination repair deficiency (HRD) useful for treatment decision making? ESMO Open. 2019;4(2):e000480.
   PubMed Web of Science ®Google Scholar
• Nichols CA, Gibson WJ, Brown MS, et al. Loss of heterozygosity of essential genes represents a widespread class of potential cancer vulnerabilities. Nat Commun. 2020 May 20;11(1):2517.
   PubMed Web of Science ®Google Scholar
• Abkevich V, Timms KM, Hennessy BT, et al. Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br J Cancer. 2012 Nov 6;107(10):1776–1782.
   PubMed Web of Science ®Google Scholar
• Barber LJ, Sandhu S, Chen L, et al. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J Pathol. 2013 Feb;229(3):422–429.
   PubMed Web of Science ®Google Scholar
• Edwards SL, Brough R, Lord CJ, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008 Feb 28;451(7182):1111–1115.
   PubMed Web of Science ®Google Scholar
• Norquist B, Wurz KA, Pennil CC, et al. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J Clin Oncol. 2011 Aug 1;29(22):3008–3015.
   PubMed Web of Science ®Google Scholar
• Sakai W, Swisher EM, Karlan BY, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008 Feb 28;451(7182):1116–1120.
   PubMed Web of Science ®Google Scholar
• Banales JM, Cardinale V, Carpino G, et al. Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016 May;13(5):261–280.
   PubMed Web of Science ®Google Scholar
• Sugawara H, Yasoshima M, Katayanagi K, et al. Relationship between interleukin-6 and proliferation and differentiation in cholangiocarcinoma. Histopathology. 1998 Aug;33(2):145–153.
   PubMed Web of Science ®Google Scholar
• Komori J, Marusawa H, Machimoto T, et al. Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma. Hepatology. 2008 Mar;47(3):888–896.
   PubMed Web of Science ®Google Scholar
• Jaiswal M, LaRusso NF, Burgart LJ, et al. Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res. 2000 Jan 1;60(1):184–190.
   PubMed Web of Science ®Google Scholar
• Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999 Apr 12;81(2):214–218.
   PubMed Web of Science ®Google Scholar
• Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell. 2010 Oct 22;40(2):179–204.
   PubMed Web of Science ®Google Scholar
• Carbone M, Yang H, Pass HI, et al. BAP1 and cancer. Nat Rev Cancer. 2013 Mar;13(3):153–159.
   PubMed Web of Science ®Google Scholar
• Saeed A, Park R, Al-Jumayli M, et al. Biologics, immunotherapy, and future directions in the treatment of advanced cholangiocarcinoma. Clin Colorectal Cancer. 2019 Jun;18(2):81–90.
   PubMed Web of Science ®Google Scholar
• Heeke AL, Pishvaian MJ, Lynce F, et al. Prevalence of homologous recombination-related gene mutations across multiple cancer types. JCO Precis Oncol. 2018;2018. doi:10.1200/PO.17.00286.
   PubMed Web of Science ®Google Scholar
• Golan T, Raitses-Gurevich M, Kelley RK, et al. Overall survival and clinical characteristics of BRCA-associated cholangiocarcinoma: a multicenter retrospective study. Oncologist. 2017 Jul;22(7):804–810.
   PubMed Web of Science ®Google Scholar
• Jusakul A, Cutcutache I, Yong CH, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 2017 Oct;7(10):1116–1135.
   PubMed Web of Science ®Google Scholar
• Ross JS, Wang K, Javle MM, et al. Comprehensive genomic profiling of biliary tract cancers to reveal tumor-specific differences and frequency of clinically relevant genomic alterations. J clin oncol. 2015;33(15_suppl):4009.
   Web of Science ®Google Scholar
• Abdel-Wahab R, Ali SM, Borad MJ, et al. Variations in DNA repair genomic alterations and tumor mutation burden in biliary tract cancer (BTC) subtypes. J clin oncol. 2018;36(4_suppl):263.
   Web of Science ®Google Scholar
• Javle MM, Catenacci DV, Jain A, et al. Precision medicine for gallbladder cancer using somatic copy number amplifications (SCNA) and DNA repair pathway gene alterations. J clin oncol. 2017;35(15_suppl):4076.
   Web of Science ®Google Scholar
• Lamarca A, Barriuso J, McNamara MG, et al. Biliary tract cancer: state of the art and potential role of DNA damage repair. Cancer Treat Rev. 2018 Nov;70:168–177.
   PubMed Web of Science ®Google Scholar
• Yu H, Pak H, Hammond-Martel I, et al. Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):285–290.
   PubMed Web of Science ®Google Scholar
• Chan-On W, Nairismagi ML, Ong CK, et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet. 2013 Dec;45(12):1474–1478.
   PubMed Web of Science ®Google Scholar
• Farshidfar F, Zheng S, Gingras MC, et al. Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles. Cell Rep. 2017 Jun 27;19(13):2878–2880.
   PubMed Web of Science ®Google Scholar
• Jiao Y, Pawlik TM, Anders RA, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013 Dec;45(12):1470–1473.
   PubMed Web of Science ®Google Scholar
• Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018 Sep 1;24(17):4154–4161.
   PubMed Web of Science ®Google Scholar
• Mosbeh A, Halfawy K, Abdel-Mageed WS, et al. Nuclear BAP1 loss is common in intrahepatic cholangiocarcinoma and a subtype of hepatocellular carcinoma but rare in pancreatic ductal adenocarcinoma. Cancer Genet. 2018 Aug;224-225:21–28.
   PubMed Web of Science ®Google Scholar
• Adeva J, Sangro B, Salati M, et al. Medical treatment for cholangiocarcinoma. Liver Int. 2019 May;39(Suppl 1):123–142.
   PubMed Web of Science ®Google Scholar
• Moeini A, Sia D, Bardeesy N, et al. Molecular pathogenesis and targeted therapies for intrahepatic cholangiocarcinoma. Clin Cancer Res. 2016 Jan 15;22(2):291–300.
   PubMed Web of Science ®Google Scholar
• Alemasova EE, Lavrik OI. Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins. Nucleic Acids Res. 2019 May 7;47(8):3811–3827.
   PubMed Web of Science ®Google Scholar
• Alvarez-Gonzalez R, Jacobson MK. Characterization of polymers of adenosine diphosphate ribose generated in vitro and in vivo. Biochemistry. 1987 Jun 2;26(11):3218–3224.
   PubMed Web of Science ®Google Scholar
• Bitler BG, Watson ZL, Wheeler LJ, et al. PARP inhibitors: clinical utility and possibilities of overcoming resistance. Gynecol Oncol. 2017 Dec;147(3):695–704.
   PubMed Web of Science ®Google Scholar
• Taylor KN, Eskander RNPARP. Inhibitors in epithelial ovarian cancer. Recent Pat Anticancer Drug Discov. 2018;13(2):145–158.
   PubMed Web of Science ®Google Scholar
• Kamaletdinova T, Fanaei-Kahrani Z, Wang ZQ. The enigmatic function of PARP1: from PARylation activity to PAR readers. Cells. 2019 Dec 12;8(12).
   PubMed Web of Science ®Google Scholar
• Ashworth A, Lord CJ, Reis-Filho JS. Genetic interactions in cancer progression and treatment. Cell. 2011 Apr 1;145(1):30–38.
   PubMed Web of Science ®Google Scholar
• Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244–250.
   PubMed Web of Science ®Google Scholar
• Mateos-Gomez PA, Gong F, Nair N, et al. Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination. Nature. 2015 Feb 12;518(7538):254–257.
   PubMed Web of Science ®Google Scholar
• Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005 Apr 14;434(7035):917–921.
   PubMed Web of Science ®Google Scholar
• Fontaine SD, Ashley GW, Houghton PJ, et al. A very long-acting Poly(ADP-ribose) polymerase inhibitor suppresses cancer cell growth in DNA repair-deficient tumor models. Cancer Res. 2020 Dec 15. doi:10.1158/0008-5472.CAN-20-1741.
   Web of Science ®Google Scholar
• Rose M, Burgess JT, O’Byrne K, et al. PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance. Front Cell Dev Biol. 2020;8:564601.
   PubMed Web of Science ®Google Scholar
• Murai J, Huang SY, Renaud A, et al. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther. 2014 Feb;13(2):433–443.
   PubMed Web of Science ®Google Scholar
• Lee JM, Ledermann JA, Kohn ECPARP. Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 2014 Jan;25(1):32–40.
   PubMed Web of Science ®Google Scholar
• Pommier Y, O’Connor MJ, De Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med. 2016 Oct 26;8(362): 362ps17.
   Web of Science ®Google Scholar
• Leo E, Johannes J, Illuzzi G, et al. Abstract LB-273: a head-to-head comparison of the properties of five clinical PARP inhibitors identifies new insights that can explain both the observed clinical efficacy and safety profiles. Cancer Res. 2018;78(13Supplement):LB–273.
   Google Scholar
• Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753–763.
   PubMed Web of Science ®Google Scholar
• Boussios S, Karathanasi A, Cooke D, et al. PARP inhibitors in ovarian cancer: the route to “Ithaca”. Diagnostics (Basel). 2019 May 18;9(2):55.
   Google Scholar
• Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636–648.
   PubMed Web of Science ®Google Scholar
• Guimbaud R, Louvet C, Bonnetain F, et al. Final results of the intergroup Ffcd-Gercor-Fnclcc 03-07 phase III study comparing two sequences of chemotherapy in advanced gastric cancers. Ann Oncol. 2010;21:250.
   Web of Science ®Google Scholar
• Silver DP, Richardson AL, Eklund AC, et al. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1145–1153.
   PubMed Web of Science ®Google Scholar
• Tassone P, Tagliaferri P, Perricelli A, et al. BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer. 2003 Apr 22;88(8):1285–1291.
   PubMed Web of Science ®Google Scholar
• Chae H, Kim D, Yoo C, et al. Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker. Eur J Cancer. 2019 Oct;120:31–39.
   PubMed Web of Science ®Google Scholar
• Zhang W, Shi J, Li R, et al. Effectiveness of olaparib treatment in a patient with gallbladder cancer with an ATM-inactivating mutation. Oncologist. 2020 May;25(5):375–379.
   PubMed Web of Science ®Google Scholar
• Gray HJ, Bell-mcguinn K, Fleming GF, et al. Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies. Gynecol Oncol. 2018 Mar;148(3):507–514.
   PubMed Web of Science ®Google Scholar
• Cheng Y, Zhang J, Qin SK, et al. Treatment with olaparib monotherapy for BRCA2-mutated refractory intrahepatic cholangiocarcinoma: a case report. Onco Targets Ther. 2018;11:5957–5962.
   PubMed Web of Science ®Google Scholar
• Xie Y, Jiang Y, Yang XB, et al. Response of BRCA1-mutated gallbladder cancer to olaparib: a case report. World J Gastroenterol. 2016 Dec 14;22(46):10254–10259.
   PubMed Web of Science ®Google Scholar
• Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509–2520.
   PubMed Web of Science ®Google Scholar
• Mouw KW, Goldberg MS, Konstantinopoulos PA, et al. DNA damage and repair biomarkers of immunotherapy response. Cancer Discov. 2017 7; Jul(7): 675–693.
   Web of Science ®Google Scholar
• Fouassier L, Marzioni M, Afonso MB, et al. Signalling networks in cholangiocarcinoma: molecular pathogenesis, targeted therapies and drug resistance. Liver Int. 2019 May;39(Suppl 1):43–62.
   PubMed Web of Science ®Google Scholar
• Kim RD, Chung V, Alese OB, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol. 2020 Jun 1;6(6):888–894.
   PubMed Web of Science ®Google Scholar
• Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020 Oct;21(10):1353–1365.
   PubMed Web of Science ®Google Scholar
• Bang YJ, Ueno M, Malka D, et al. Pembrolizumab (pembro) for advanced biliary adenocarcinoma: results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies. J clin oncol. 2019;37(15_suppl):4079.
   Web of Science ®Google Scholar
• Ioka T, Ueno M, Oh DY, et al. Evaluation of safety and tolerability of durvalumab (D) with or without tremelimumab (T) in patients (pts) with biliary tract cancer (BTC). J clin oncol. 2019;37(4_suppl):387.
   Web of Science ®Google Scholar
• Ueno M, Ikeda M, Morizane C, et al. Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: a non-randomised, multicentre, open-label, phase 1 study. Lancet Gastroenterol Hepatol. 2019 Aug;4(8):611–621.
   PubMed Web of Science ®Google Scholar
• Mahipal A, Kommalapati A, Tella SH, et al. Novel targeted treatment options for advanced cholangiocarcinoma. Expert Opin Investig Drugs. 2018 Sep;27(9):709–720.
   PubMed Web of Science ®Google Scholar
• Boscoe AN, Rolland C, Kelley RK. Frequency and prognostic significance of isocitrate dehydrogenase 1 mutations in cholangiocarcinoma: a systematic literature review. J Gastrointest Oncol. 2019 Aug;10(4):751–765.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Stein EM, De Botton S, et al. Durable remissions with Ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386–2398.
   PubMed Web of Science ®Google Scholar
• Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug 10;130(6):722–731.
   PubMed Web of Science ®Google Scholar
• Kumareswaran R, Ludkovski O, Meng A, et al. Chronic hypoxia compromises repair of DNA double-strand breaks to drive genetic instability. J Cell Sci. 2012 Jan 1;125(Pt 1):189–199.
   PubMed Web of Science ®Google Scholar
• Tentori L, Lacal PM, Muzi A, et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur J Cancer. 2007 Sep;43(14):2124–2133.
   PubMed Web of Science ®Google Scholar
• Bindra RS, Gibson SL, Meng A, et al. Hypoxia-induced down-regulation of BRCA1 expression by E2Fs. Cancer Res. 2005 Dec 15;65(24):11597–11604.
   PubMed Web of Science ®Google Scholar
• Bindra RS, Schaffer PJ, Meng A, et al. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol. 2004 Oct;24(19):8504–8518.
   PubMed Web of Science ®Google Scholar
• Lim JJ, Yang K, Taylor-Harding B, et al. VEGFR3 inhibition chemosensitizes ovarian cancer stemlike cells through down-regulation of BRCA1 and BRCA2. Neoplasia. 2014 Apr;16(4):343–53 e1-2.
   PubMed Web of Science ®Google Scholar
• Liu JF, Barry WT, Birrer M, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014 Oct;15(11):1207–1214.
   PubMed Web of Science ®Google Scholar
• Matulonis UA, Wulf GM, Barry WT, et al. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer. Ann Oncol. 2017 Mar 1;28(3):512–518.
   PubMed Web of Science ®Google Scholar
• Mo W, Liu Q, Lin CC, et al. mTOR inhibitors suppress homologous recombination repair and synergize with PARP inhibitors via regulating SUV39H1 in BRCA-proficient triple-negative breast cancer. Clin Cancer Res. 2016 Apr 1;22(7):1699–1712.
   PubMed Web of Science ®Google Scholar
• Boussios S, Karihtala P, Moschetta M, et al. Combined strategies with poly (ADP-Ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer: a literature review. Diagnostics (Basel). 2019 Aug 1;9(3):87.
   Google Scholar
• Yap TA, Plummer R, Azad NS, et al. The DNA damaging revolution: PARP inhibitors and beyond. Am Soc Clin Oncol Educ Book. 2019 Jan;39(39):185–195.
   PubMedGoogle Scholar
• Kurnit KC, Meric-Bernstam F, Hess K, et al. Abstract CT020: phase I dose escalation of olaparib (PARP inhibitor) and selumetinib (MEK Inhibitor) combination in solid tumors with Ras pathway alterations. Cancer Res. 2019;79(13Supplement):CT020.
   Google Scholar
• Westin SN, Litton JK, Williams RA, et al. Phase I trial of olaparib (PARP inhibitor) and vistusertib (mTORC1/2 inhibitor) in recurrent endometrial, ovarian and triple negative breast cancer. J clin oncol. 2018;36(15_suppl):5504.
   Web of Science ®Google Scholar
• Yap TA, Kristeleit R, Michalarea V, et al. Phase I trial of the PARP inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2- and non-BRCA1/2-mutant cancers. Cancer Discov. 2020 Oct;10(10):1528–1543.
   PubMed Web of Science ®Google Scholar