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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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The emerging role of PARP inhibitors in prostate cancer

Marco Stellato1, Valentina Guadalupi1, Pierangela Sepe1

  • 1Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori , Milan, Italy.

Expert Review of Anticancer Therapy
|August 8, 2020
PubMed
Abstract

Insights

Homologous recombination repair (HRR) gene mutations are emerging in prostate cancer. Poly (ADP-ribose) polymerase inhibitors (PARPi) show promise in treating metastatic castration-resistant prostate cancer (mCRPC), with combination therapies under investigation.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Emerging interest in homologous recombination repair (HRR) gene mutations in prostate cancer.
  • HRR gene mutations, including BRCA1, BRCA2, and ATM, are found in prostate cancer at varying rates.
  • Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) target DNA repair mechanisms.

Purpose of the Study:

  • To review the role of HRR mutations and PARP inhibition in prostate cancer.
  • To discuss the clinical development and efficacy of various PARPi in metastatic castration-resistant prostate cancer (mCRPC).
  • To evaluate the potential of combination therapies involving PARPi.

Main Methods:

  • Review of current literature on HRR mutations and PARPi in prostate cancer.
  • Analysis of clinical trial data for PARPi (olaparib, talazoparib, niraparib, rucaparib, veliparib) in mCRPC.
  • Assessment of preliminary results for combination therapies.

Main Results:

  • Olaparib's efficacy in mCRPC is validated by a Phase III trial.
  • Rucaparib and niraparib show promising early results in Phase II trials.
  • Combination therapy with PARPi and new hormonal therapy demonstrates encouraging outcomes.

Conclusions:

  • PARPi are established treatments for mCRPC.
  • Combination therapies with PARPi and hormonal agents have a strong biological basis and promising early results.
  • Further validation in randomized Phase III trials is necessary to integrate PARPi into standard clinical practice.
Keywords:
BRCA-1BRCA-2HRR genesPARPimetastatic castration resistance prostatic cancerniraparibolaparibrucaparibtalazoparibveliparib

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