Development of PARP inhibitors in advanced prostate cancer.
Maria Teresa BourlonPaola ValdezElena CastroPublished in: Therapeutic advances in medical oncology (2024)
The relatively high prevalence of alterations in the homologous recombination repair (HRR) pathway described in advanced prostate cancer provides a unique opportunity to develop therapeutic strategies that take advantage of the decreased tumor ability to repair DNA damage. Poly ADP-ribose polymerase (PARP) inhibitors have been demonstrated to improve the outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients with HRR defects, particularly in those with BRCA1/2 alterations. To expand the benefit of PARPi to patients without detectable HRR alterations, multiple studies are addressing potential synergies between PARP inhibition (PARPi) and androgen receptor pathway inhibitors (ARSi), radiation, radioligand therapy, chemotherapy, or immunotherapy, and these strategies are also being evaluated in the hormone-sensitive setting. In this review, we summarize the development of PARPi in prostate cancer, the potential synergies, and combinations being investigated as well as the future directions of PARPi for the management of the disease.
Keyphrases
- dna damage
- prostate cancer
- dna repair
- radical prostatectomy
- oxidative stress
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- squamous cell carcinoma
- small cell lung cancer
- human health
- prognostic factors
- peritoneal dialysis
- adipose tissue
- radiation therapy
- current status
- radiation induced
- patient reported
- case control
- single molecule