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BRCAness and prostate cancer: diagnostic and therapeutic considerations

Prostate Cancer and Prostatic Diseases volume 21, pages 488–498 (2018)Cite this article

Subjects

Abstract

Background:

Recent advances in genetic sequencing and recent studies focusing on the broader use of Poly ADP Ribose polymerase (PARP) inhibitors have led to an upsurge of interest in DNA repair mutations as they relate to prostate cancer.

Methods:

This review outlines ongoing studies and recent publications as they relate to the prevalence and detection of DNA repair mutations in metastatic prostate cancer. The detection of these mutations through multiple diagnostic approaches is discussed, including germline sequencing, somatic sequencing, cell-free DNA assays, and circulating tumor cell assays. The clinical course of patients with prostate cancer and DNA repair gene mutations is explored in addition to therapeutic strategies for this population.

Conclusions:

In men with metastatic prostate cancer, it is reasonable to obtain germline genetic sequencing as well as somatic tumor genomic sequencing to help guide further treatment decisions that may include PARP inhibitors or carboplatin in the future. In the future, in men with metastatic castrate resistant prostate cancer with progression on PARP inhibitors, cell-free DNA sequencing may help elucidate mechanisms of resistance, which include reversion mutations.

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Acknowledgements

Dr. Dhawan has received funding from 2016–2017 from the Prescient grant NIH TL1, Grant Number UL1 TR001872.

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Authors and Affiliations

  1. Genitourinary Medical Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94115, USA

    Mallika Dhawan & Charles J. Ryan

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  1. Mallika Dhawan
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Correspondence to Charles J. Ryan.

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Conflict of interest

Dr. Ryan has received research support from Clovis Oncology and has a consultant/advisory role with Janssen. Dr. Dhawan has served as a consultant for Driver.

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Dhawan, M., Ryan, C.J. BRCAness and prostate cancer: diagnostic and therapeutic considerations. Prostate Cancer Prostatic Dis 21, 488–498 (2018). https://doi.org/10.1038/s41391-018-0069-2

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