TY - JOUR
T1 - Castration-resistant prostate cancer
T2 - Latest evidence and therapeutic implications
AU - Suzman, Daniel L.
AU - Antonarakis, Emmanuel S.
N1 - Funding Information:
E.S.A. is partially funded by NIH grant P30 CA006973.
Funding Information:
D.S. declares no conflicts of interest in preparing this article. E.S.A. is a paid consultant/advisor to Janssen Biotech, and has received research funding from Janssen. E.S.A. is also a paid consultant/advisor to Dendreon and Sanofi.
PY - 2014/7
Y1 - 2014/7
N2 - Medical oncologists who treat men with castration-resistant prostate cancer (CRPC) have seen an abundance of new agents approved by the United States Food and Drug Administration in the last decade for a disease that was previously difficult to treat after becoming resistant to androgen-deprivation therapy. Advances in understanding of the mechanisms of castration-resistance and prostate cancer progression have highlighted several pathways and targets that appear promising to better treat CRPC. As the majority of CRPC appears to continue to rely on the androgen receptor for growth and progression, several of these agents directly or indirectly target the androgen receptor. A novel microtubule-targeted agent, cabazitaxel, has demonstrated an overall survival benefit following progression on docetaxel. Other agents target tumor immunogenicity and immune checkpoint pathways to attempt to harness the host immune system. The recently approved radiopharmaceutical, radium-223 dichloride, has demonstrated impressive results in patients with extensive bony metastases with minimal toxicity. Lastly, further understanding of the pathways underlying CRPC progression has led to late-phase clinical trials with the novel agents: custirsen, tasquinimod and cabozantinib. This article reviews the approved therapies for CRPC, the agents currently in late-phase clinical trials, and notable early-phase trials of novel therapies and their combinations, with particular attention to trials incorporating novel biomarkers and intermediate endpoints to better identify those men who may or may not benefit from specific therapies.
AB - Medical oncologists who treat men with castration-resistant prostate cancer (CRPC) have seen an abundance of new agents approved by the United States Food and Drug Administration in the last decade for a disease that was previously difficult to treat after becoming resistant to androgen-deprivation therapy. Advances in understanding of the mechanisms of castration-resistance and prostate cancer progression have highlighted several pathways and targets that appear promising to better treat CRPC. As the majority of CRPC appears to continue to rely on the androgen receptor for growth and progression, several of these agents directly or indirectly target the androgen receptor. A novel microtubule-targeted agent, cabazitaxel, has demonstrated an overall survival benefit following progression on docetaxel. Other agents target tumor immunogenicity and immune checkpoint pathways to attempt to harness the host immune system. The recently approved radiopharmaceutical, radium-223 dichloride, has demonstrated impressive results in patients with extensive bony metastases with minimal toxicity. Lastly, further understanding of the pathways underlying CRPC progression has led to late-phase clinical trials with the novel agents: custirsen, tasquinimod and cabozantinib. This article reviews the approved therapies for CRPC, the agents currently in late-phase clinical trials, and notable early-phase trials of novel therapies and their combinations, with particular attention to trials incorporating novel biomarkers and intermediate endpoints to better identify those men who may or may not benefit from specific therapies.
KW - cabozantinib; castration-resistant prostate cancer
KW - custirsen
KW - radium-223 dichloride
KW - tasquinimod
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U2 - 10.1177/1758834014529176
DO - 10.1177/1758834014529176
M3 - Review article
C2 - 25057303
AN - SCOPUS:84904800824
VL - 6
SP - 167
EP - 179
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
SN - 1758-8340
IS - 4
ER -