RESUMEN
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.
Asunto(s)
Proteína BRCA1 , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Femenino , Humanos , Proteína BRCA1/genética , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Medicina de Precisión , Proteína BRCA2/genética , Poli(ADP-Ribosa) PolimerasasRESUMEN
The search for dependable molecular biomarkers to enhance routine clinical practice is a compelling challenge across all oncology fields. Urothelial bladder carcinoma, known for its significant heterogeneity, presents difficulties in predicting responses to systemic therapies and outcomes post-radical cystectomy. Recent advancements in molecular cancer biology offer promising avenues to understand the disease's biology and identify emerging predictive biomarkers. Stratifying patients based on their recurrence risk post-curative treatment or predicting the efficacy of conventional and targeted therapies could catalyze personalized treatment selection and disease surveillance. Despite progress, reliable molecular biomarkers to forecast responses to systemic agents, in neoadjuvant, adjuvant, or palliative treatment settings, are still lacking, underscoring an urgent unmet need. This review aims to delve into the utilization of current and emerging molecular signatures across various stages of urothelial bladder carcinoma to predict responses to systemic therapy.