Publications by authors named "C M Bertan"
Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.
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- - PARP inhibitors show promise in treating castration-resistant prostate cancer (CRPC) with homologous recombination repair (HRR) defects, but the reasons behind resistance are not completely understood.
- - A study from the TOPARP-B trial found that 79% of BRCA2/PALB2-mutated tumors exhibited reversion mutations at the end of treatment, with many related to POLQ-mediated DNA repair mechanisms.
- - In cases of BRCA2 homozygous deletions, rare subclones lacking the BRCA2 deletion are selected for after PARP inhibitor treatment, indicating the necessity for restored HRR function in developing resistance.
Article Synopsis
- * BCL2, an anti-apoptotic protein, is upregulated in these aggressive prostate cancers, which presents a potential target for therapy and highlights the importance of studying its expression in metastatic CRPC (mCRPC).
- * Research shows that BCL2 is more prevalent in AR-negative mCRPC and is linked to poorer survival outcomes; also, its regulation involves DNA methylation and a transcription factor called ASCL1, suggesting the need for combination therapies to improve treatment efficacy.
BACKGROUNDClinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome, and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.
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- The study investigates the effectiveness of the AKT inhibitor capivasertib when combined with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who did not respond well to prior treatments with abiraterone acetate and docetaxel.
- Conducted as a double-blind, randomized phase 2 trial with 100 men, the primary focus was on the composite response rate, which showed no significant improvement with the combination treatment compared to placebo.
- Analysis revealed that patients with PTEN loss had poorer overall survival regardless of treatment, with common side effects including diarrhea and fatigue, indicating that while the combination was tolerable, it did not enhance treatment outcomes.