@article{42ba74a75bcf4423bf4afe2302f629f7,
title = "Effect of DNA damage response mutations on prostate cancer prognosis: a systematic review",
abstract = "The prognosis of men with prostate cancer (PC) with mutations in DNA damage response (DDR) genes undergoing different treatments is unclear. This systematic review compared clinical outcomes in PC patients with DDR mutations (DDR+) versus no mutations (DDR-). 14 resources plus gray literature were searched for studies in PC and subgroups (castration-resistant PC, metastatic PC and metastatic castration-resistant PC) by DDR gene (ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) mutation status. From 11,648 records, 26 studies were included. For mCRPC, six studies reported comparative efficacy for key outcomes. Improvements in several clinical outcomes were observed for DDR+ (vs DDR-) after PARP inhibitor therapy or immunotherapy. DDR+ PC patients may have improved outcomes depending on the treatment they undergo.",
keywords = "ATM, BRCA1, BRCA2, DDR, DNA damage response, genes, mutation, outcome, prostate cancer, therapy, BRCA MUTATIONS, REPAIR, RADIATION, ASSOCIATION, VARIANTS, TOXICITY, THERAPY, RISK, MEN, POLYMORPHISMS",
author = "Swift, {Stephanie L.} and Lang, {Shona H.} and Heath White and Kate Misso and Jos Kleijnen and Quek, {Ruben G. W.}",
note = "Funding Information: Editorial and medical writing support was provided by Ying Jean, Gautam Bijur, Mary Kacillas and Joshua Safran at Ashfield Healthcare Communications, Middletown, CT, USA, which was funded by Pfizer. Funding Information: This study was sponsored and funded by Pfizer. All the authors had full access to all of the data in this study and take responsibility for the integrity of the data and accuracy of the data analysis. SL Swift, SH Lang, H White, K Misso and J Kleijnen are employees of KSR Ltd, who received financial support from Pfizer in connection with the development of this manuscript; they have no other conflicts of interest. RGW Quek is an employee of Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: {\textcopyright} 2019 {\textcopyright} 2019 Stephanie L. Swift Lay abstract Genes involved in the DNA damage response (DDR) are mutated in around one in five men with prostate cancer (PC). While new treatment guidelines recommend that advanced PC patients be screened for DDR gene mutations to assess eligibility for relevant clinical trials, it is largely unclear how these mutations impact clinical outcomes following different treatments. After systematically reviewing the literature, current evidence suggests that patients with advanced PC and DDR mutations have better outcomes following treatment with PARP inhibitors or immunotherapies compared with patients without DDR mutations. Overall, this suggests that testing PC patients for DDR mutations may improve prognosis. {\textcopyright} 2019 {\textcopyright} 2019 Stephanie L. Swift.",
year = "2019",
month = oct,
doi = "10.2217/fon-2019-0298",
language = "English",
volume = "15",
pages = "3283--3303",
journal = "Future Oncology",
issn = "1479-6694",
publisher = "Routledge/Taylor & Francis Group",
number = "28",
}