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Beyond Breast and Ovarian Cancers: PARP Inhibitors for BRCA Mutation-Associated and BRCA-Like Solid Tumors

Overview
Journal Front Oncol
Specialty Oncology
Date 2014 Mar 12
PMID 24616882
Citations 53
Authors
Affiliations
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Abstract

Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown clinical activity in patients with germline BRCA1/2 mutation (gBRCAm)-associated breast and ovarian cancers. Accumulating evidence suggests that PARPi may have a wider application in the treatment of cancers defective in DNA damage repair pathways, such as prostate, lung, endometrial, and pancreatic cancers. Several PARPi are currently in phase I/II clinical investigation, as single-agents and/or combination therapy in these solid tumors. Understanding more about the molecular abnormalities involved in BRCA-like phenotype in solid tumors beyond breast and ovarian cancers, exploring novel therapeutic trial strategies and drug combinations, and defining potential predictive biomarkers are critical to expanding the scope of PARPi therapy. This will improve clinical outcome in advanced solid tumors. Here, we briefly review the preclinical data and clinical development of PARPi, and discuss its future development in solid tumors beyond gBRCAm-associated breast and ovarian cancers.

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References
1.
Samol J, Ranson M, Scott E, Macpherson E, Carmichael J, Thomas A . Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. Invest New Drugs. 2011; 30(4):1493-500. DOI: 10.1007/s10637-011-9682-9. View

2.
Bernstein C, Bernstein H, Payne C, Garewal H . DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat Res. 2002; 511(2):145-78. DOI: 10.1016/s1383-5742(02)00009-1. View

3.
Vorechovsky I, Luo L, Ortmann E, Steinmann D, Dork T . Missense mutations at ATM gene and cancer risk. Lancet. 1999; 353(9160):1276. DOI: 10.1016/s0140-6736(05)75199-0. View

4.
BELL D, Varley J, Szydlo T, Kang D, Wahrer D, Shannon K . Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 2000; 286(5449):2528-31. DOI: 10.1126/science.286.5449.2528. View

5.
Esteller M, Silva J, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E . Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000; 92(7):564-9. DOI: 10.1093/jnci/92.7.564. View