[Poly(ADP-ribose) polymerase (PARP-)inhibitors as genetically based precision therapy in metastatic...

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) treatment has advanced with the introduction of PARP inhibitors.
• Current indications necessitate BRCA1/2 gene mutations and prior hormonal therapy.

Purpose of the Study:

• To review the molecular basis of PARP inhibition in mCRPC.
• To summarize clinical trials investigating PARP inhibitors, including combination strategies.

Main Methods:

• Literature review of molecular mechanisms.
• Summary of ongoing and completed clinical trials for PARP inhibitors in mCRPC.

Main Results:

• PARP inhibitors represent a new therapeutic class for mCRPC since November 2020.
• Positive clinical trial data support BRCA1/2 mutation-dependent PARP inhibition.
• A significant proportion of mCRPC patients harbor actionable mutations.

Conclusions:

• Personalized therapy targeting BRCA1/2 mutations with PARP inhibitors is effective for mCRPC.
• This approach is recognized in updated clinical guidelines, including S3 guidelines.