BERKELEY, CA (UroToday.com) - Currently, there are no effective treatment regimens for patients with metastatic prostate cancer. Additional clinical trials are underway to study the efficiency of novel therapeutic agents and drug combinations. Preclinical studies have revealed potential novel therapeutic targets.
However the complexity and heterogeneity of prostate tumors represents a critical challenge to the development of new effective therapies with minimal toxicity for advanced prostate cancer. Therefore multi-drug combinations to target several pathways that govern the development of castration-resistant prostate cancer may have advantages over the treatments using single drugs. However, given the potential increased adverse effect caused by multi-drug combinations, there is an urgent need to reduce off-target effects of multi-drugs in use or under development. AR plays a vital role in both hormone dependent and castration resistant PCa, therefore targeting recently identified components of the AR signaling network may represent a novel approach. Clinical trials of anti-angiogenic factors including inhibitors that target VEGF, VEGFR1 or MMP inhibitors for treatment of castration resistant PCas have been disappointing thus far. This is likely due to the lack of specificity these drugs in targeting PCa cells. Therefore, there is an urgent need to improve the selectivity of current drugs to specifically target angiogenic and metastatic pathways in tumor cells. Such multi-drug combinations that selectively target the tumor cells but not recognize the normal cells may represent the novel therapies for metastatic PCa.
One of the most important drugs for the treatment of castration resistant prostate cancer is the potent, irreversible cyp17 inhibitor abiraterone acetate; abiraterone is a selective inhibitor of CYP17, an enzyme required for androgen biosynthesis in the testes, adrenal glands, and prostate. Abiraterone Acetate was approved by U.S FDA in April 2011. The ability of abiraterone to block systemic androgen synthesis represents an alternative therapeutic strategy to overcome AR-related mechanisms of ADT resistance as abiraterone inhibition of CYP17 starves the prostate of androgens. A recent study showed that abiraterone prolonged survival in patients with prior docetaxel chemotherapy. These exciting findings encourage the development of novel approaches to treat metastatic PCa.
Finally, recent advances in the identification and characterisation of putative prostate cancer stem cells are an important clinical development. Such cells represent novel therapeutics target for the next generation of PCa treatments. Prostate cancer stem cells likely contribute to the observed heterogeneity of prostate tumors, PCa metastasis. Therefore the identification and targeting these subsets of prostate cancer cells may have great potential for the effective prevention and treatment of metastatic PCa. Advanced, genome-wide screening technologies and proteomics will play an important role in the discovery of the novel targets and biomarkers to determine the endpoints of treatment. The ultimate therapeutic goal is to develop and apply targeted therapies that distinguish between malignant and normal tissues.
Written by:
Jenny Liao Persson, PhD., Et Al. as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Clinical trial update and novel therapeutic approaches for metastatic prostate cancer - Abstract
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