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PARP inhibition — not all gene mutations are created equal

Nature Reviews Urology volume 16, pages 4–6 (2019)Cite this article

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Preliminary results from TRITON2 demonstrate efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in ~50% of patients with metastatic castration-resistant prostate cancer and inactivation of BRCA1/BRCA2. However, those with ATM and CDK12 mutations do not seem to benefit. An improved homologous recombination deficiency test must be developed and alternative treatments defined for these subsets of patients.

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Fig. 1: Clinical benefit of PARP inhibition might differ by mutation patterns of genes implicated in HR DNA repair.

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Acknowledgements

This work was partially supported by NIH Cancer Center Support Grant P30 CA006973, the Department of Defense (DOD) grant W81XWH-16-PCRP-CCRSA, NIH grant R01 CA185297, and US Department of Defense Prostate Cancer Research Program grant W81XWH-15-2-0050, and the Patrick C. Walsh Research Fund.

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Authors and Affiliations

  1. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jun Luo

  2. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Emmanuel S. Antonarakis

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  1. Jun Luo
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Correspondence to Jun Luo.

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Competing interests

E.S.A. is a paid consultant/adviser to Janssen, Astellas, Sanofi, Dendreon, Medivation, AstraZeneca, Clovis, and Merck; has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck; and is the co-inventor of a biomarker technology that has been licensed to Qiagen. J.L. has served as a paid consultant and adviser for Sun Pharma, Janssen, and Sanofi; has received research funding to his institution from Orion, Astellas, Sanofi, Constellation, and Gilead; and is a co-inventor of a technology that has been licensed to A&G, Tokai, and Qiagen.

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Luo, J., Antonarakis, E.S. PARP inhibition — not all gene mutations are created equal. Nat Rev Urol 16, 4–6 (2019). https://doi.org/10.1038/s41585-018-0129-3

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