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Precision Medicine in Castration-Resistant Prostate Cancer: Advances, Challenges, and the Landscape of PARPi Therapy-A Narrative Review.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Feb 11; Vol. 25 (4). Date of Electronic Publication: 2024 Feb 11. - Publication Year :
- 2024
-
Abstract
- After recent approvals, poly-adenosine diphosphate [ADP]-ribose polymerase inhibitors (PARPis) have emerged as a frontline treatment for metastatic castration-resistant prostate cancer (mCRPC). Unlike their restricted use in breast or ovarian cancers, where approval is limited to those with BRCA1/2 alterations, PARPis in mCRPC are applied across a broader spectrum of genetic aberrations. Key findings from the phase III PROPEL trial suggest that PARPis' accessibility may broaden, even without mandatory testing. An increasing body of evidence underscores the importance of distinct alterations in homologous recombination repair (HRR) genes, revealing unique sensitivities to PARPis. Nonetheless, despite the initial effectiveness of PARPis in treating BRCA-mutated tumors, resistance to therapy is frequently encountered. This review aims to discuss patient stratification based on biomarkers and genetic signatures, offering insights into the nuances of first-line PARPis' efficacy in the intricate landscape of mCRPC.
- Subjects :
- Male
Female
Humans
Poly(ADP-ribose) Polymerase Inhibitors pharmacology
Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
Precision Medicine
BRCA2 Protein genetics
Poly(ADP-ribose) Polymerases
BRCA1 Protein genetics
Prostatic Neoplasms, Castration-Resistant drug therapy
Prostatic Neoplasms, Castration-Resistant genetics
Prostatic Neoplasms, Castration-Resistant pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38396858
- Full Text :
- https://doi.org/10.3390/ijms25042184