Novel targeted therapeutics for metastatic castration-resistant prostate cancer.
Virtually all patients that succumb to prostate cancer die of metastatic castration-resistant disease. Although docetaxel is the standard of care for these patients and is associated with a modest prolongation of survival, there is an urgent need for novel treatment strategies for metastatic prostate cancer. In the last several years, great strides have been made in our understanding of the biological and molecular mechanisms driving prostate cancer growth and progression, and this has resulted in widespread clinical testing of numerous new targeted therapies. This review discusses some of the key therapeutic agents that have emerged for the treatment of metastatic castration-resistant prostate cancer in the last 5years, with an emphasis on both molecular targets and clinical trial design. These agents include mammalian target of rapamycin (mTOR) pathway inhibitors, anti-angiogenic drugs, epidermal growth factor receptor (EGFR) inhibitors, insulin-like growth factor (IGF) pathway inhibitors, apoptosis-inducing drugs, endothelin receptor antagonists, receptor activator of nuclear factor kappaB (RANK) ligand inhibitors, vitamin D analogues, cytochrome P17 enzyme inhibitors, androgen receptor modulators, epigenetic therapies, vaccine therapies, and cytotoxic T lymphocyte-associated antigen (CTLA)-4 blocking agents.
Antonarakis
Emmanuel S
ES
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, United States. eantona1@jhmi.edu
Carducci
Michael A
MA
Eisenberger
Mario A
MA
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D007167:Immunotherapy; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D008297:Male; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases
D020533:Angiogenesis Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; C546842:MTOR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases