The hurdle of antiandrogen drug resistance: drug design strategies

Introduction: Prostate cancer is the second most common cancer death in men after lung cancer, due to distant metastases. While distant prostate cancer is typically castrate resistant, it is not necessarily androgen independent. For this reason, a review of the literature regarding the pathways involved in androgen signaling and therapeutic regimens to treat distant metastases is beneficial to increasing the survival rate of prostate cancer patients. Areas covered: In this article, the author reviews the literature from the past decade covering metastatic hormone refractory prostate cancer with the aim to examine and identify pathways, therapeutic targets and current therapies for treating castrate-resistant disease. As this area is lacking, the author aims to provide the reader with knowledge of the molecular consequences of castrate resistant prostate cancer, the current treatment paradigms and future directions. Expert opinion: While there have been advances in the treatment of castrate resistant prostate cancer, only minimal advances have been made in overall survival rate. Due to aberrant mutations and activation in the androgen receptor gene, and the complexity of cell signaling within prostate cancer, the androgen receptor should remain a main target for drug discovery efforts. This author believes that designing compounds that will reduce the activation of the androgen receptor may hold the key to a cure in the future.