Emerging cell cycle inhibitors for treating metastatic castration-resistant prostate cancer.

Emerging cell cycle inhibitors for treating metastatic castration-resistant prostate cancer. Expert Opin Emerg Drugs. 2018 Nov 13;: Authors: Batra A, Winquist E Abstract Introduction Disease progression despite androgen suppression defines lethal castration-resistant prostate cancer (CRPC). Most of these cancers remain androgen receptor (AR)-signalling dependent. Therapy for metastatic CRPC includes abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, and radium-223. However, survival remains modest for men with progressive disease despite AR-targeted therapy and docetaxel, and therefore novel treatments are needed. Areas covered Recent evidence of genomic heterogeneity and sensitivity to PARP inhibitors supports investigation of targeted agents in CRPC. Cell cycle inhibitors are therefore logical molecules to investigate. Review of the current literature identified cell cycle inhibitors under study in early phase clinical trials targeting the G1 (palbociclib, ribociclib, AZD-5363, ipatasertib), S (M-6620, prexasertib), G2 (adavosertib) and M (alisertib) phases of the cell cycle. Expert opinion Strategies combining cell cycle inhibitors with active agents in CRPC are most likely to have clinical impact with CDK4/6 and Wee1 inhibitors appearing most promising. Identification of predictive biomarkers may be essential and currently trials are testing circulating cell-free DNA as an approach. Incremental toxicities su...
Source: Expert Opinion on Emerging Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Emerg Drugs Source Type: research