DNA repair deficiency is common in advanced prostate cancer: New therapeutic opportunities

Mallika Dhawan, Charles J. Ryan, Alan Ashworth

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Advances in DNA sequencing technology have created a wealth of information regarding the genomic landscape of prostate cancer. It had been thought that BRCA1 and BRCA2 mutations were associated with only a small fraction of prostate cancer cases. However, recent genomic analysis has revealed that germline or somatic inactivating mutations in BRCA1 or BRCA2, or other genes involved in the homologous recombination (HR) pathway of DNA repair collectively occur in as much as 20%–25% of advanced prostate cancers. A synthetic lethal therapeutic approach using poly(ADP-ribose) polymerase inhibitor therapy has been developed for BRCA mutant- and HR deficient-related cancers (those with “BRCAness”) and is being studied in multiple clinical trials. This article discusses the current understanding of the genomic landscape of prostate cancer, focusing on the occurrence of DNA repair mutations and the therapeutic opportunities that this presents.

Original languageEnglish (US)
Pages (from-to)940-945
Number of pages6
JournalOncologist
Volume21
Issue number8
DOIs
StatePublished - Aug 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© AlphaMed Press 2016.

Keywords

  • BRCA
  • DNA repair
  • PARP inhibitors
  • Prostate cancer

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