Clinical Trial Update and Novel Therapeutic Approaches for Metastatic Prostate Cancer

R.      Larsson; N.      P. Mongan; M.      Johansson; L.      Shcherbina; P.-A.      Abrahamsson; L.      J. Gudas; O.      Sterner; J.      L. Persson

Abstract

Recurrent prostate cancer (PCa) remains a major clinical challenge. Invasive and metastatic PCa lesions often exhibit a partial and time-limited response to therapy before the cancer progresses and the patient succumbs to the disease. Despite recent advances in early diagnosis and treatment, approximately one-third of treated patients will relapse and become resistant to currently available treatments. In this review we evaluate current treatment practices and recent advances in therapy for localized prostate malignancy and advanced, metastatic prostate cancer. Some of the promising new drugs for PCa treatment include MDV3100, an androgen receptor (AR) antagonist that prevents androgens from binding to the AR and nuclear translocation and co-activator recruitment of the ligand-receptor complex; abiraterone, an orally administered drug that irreversibly inhibits a rate-limiting enzyme in androgen biosynthesis, CYP17; and several newer cytotoxic drugs (epothilones, satraplatin). Key new insights are that cancer stem cells play a role in PCa and that PCa cells are dependent on the AR for proliferation, even in the hormone refractory state of the disease. We also discuss potential molecular targets for new drug candidates for the treatment of metastatic PCa.

Keywords: Androgen receptor, androgen, angiogenesis, antitumor efficacy, cancer targets, castration resistant prostate cancer, clinical trials, metastases, molecular mechanisms, multi-drug combinations, neo-adjuvant setting, Prostate cancer, therapeutic approaches