Current opinion in oncology
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The review examines recent advances in second-line hormonal therapy for the treatment of castrate-resistant prostate cancer (CRPC). ⋯ Novel inhibitors of extra-gonadal androgen synthesis and androgen receptor function demonstrate the continued importance of androgen signaling in CRPC. These agents have improved clinical outcomes for patients with metastatic CRPC.
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The success of poly(ADP-ribose) polymerase inhibition in BRCA1 or BRCA2 deficient tumors as an anticancer strategy provided proof-of-concept for a synthetic lethality approach in oncology. There is therefore now active interest in expanding this approach to include other agents targeting the DNA damage response (DDR). We review lessons learnt from the development of inhibitors against DNA damage response mechanisms and envision the future of DNA repair inhibition in oncology. ⋯ There remains great enthusiasm in oncology practice for pursuing the strategy of synthetic lethality. The future development of antitumor agents targeting the DDR should include detailed correlative biomarker work within early phase clinical studies wherever possible, with clear attempts to identify doses at which robust target modulation is observed.