Alterations in BRCA2 as Determinants of Therapy Response in Prostate Cancer

Mia Hofstad, Emily Y. Huang, Andrea Woods, Yi Yin, Neil B Desai, Ganesh V. Raj

Research output: Contribution to journalArticlepeer-review


Prostate cancer (PCa) is one of the leading causes of cancer diagnoses and cancer-related deaths in the United States. Mutations or deletions in the genes involved in the DNA Damage Response (DDR) are common in aggressive primary PCa (germline alterations) and further enriched in advanced therapy-resistant PCa (somatic alterations). Among the DDR genes, BRCA2 is the most commonly altered (~13%) in advanced therapy-resistant PCa. Patients with BRCA2-altered PCas are exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis). Indeed, two PARPis-olaparib and rucaparib have recently gained FDA approval for the treatment of advanced PCas harboring a BRCA2 mutation. This review seeks to explore the role of BRCA2 in DNA damage repair, the pathogenesis and progression of BRCA2 mutant PCa, and the utility of radiation therapy, targeted therapies, and platinum-based chemotherapies for patients with BRCA2 alterations.

Original languageEnglish (US)
JournalCritical reviews in oncogenesis
Issue number1
StatePublished - 2022


  • BRCA2 mutations
  • PARP inhibitors
  • platinums
  • prostate cancer
  • radiation therapy

ASJC Scopus subject areas

  • Medicine(all)


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