Terada Naoki, Akamatsu Shusuke, Kobayashi Takashi, Inoue Takahiro, Ogawa Osamu, Antonarakis Emmanuel S
Department of Urology, Kyoto University, Kyoto, Japan.
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans Street, CRB1-1M45, Baltimore, MD 21287, USA.
Ther Adv Med Oncol. 2017 Aug;9(8):565-573. doi: 10.1177/1758834017719215. Epub 2017 Jul 5.
Advances in our understanding of the mechanisms driving castration-resistant prostate cancer have promoted the development of several new drugs including androgen receptor-directed therapy and chemotherapy. Concomitant docetaxel treatment at the beginning of hormonal therapy for metastatic prostate cancer has resulted in longer overall survival than with hormonal therapy alone. Elucidating an appropriate treatment sequence using these therapies is important for maximizing clinical benefit in castration-sensitive and castration-resistant prostate cancer patients. The development of advanced high-throughput 'omics' technology has enabled the use of novel markers to guide prognosis and treatment of this disease. In this review, we outline the genomic landscape of prostate cancer and the molecular mechanisms of castration-resistant progression, and how these affect the development of new drugs, and their clinical implications for selecting treatment sequence. We also discuss many of the potential tissue-based or liquid biomarkers that may soon enter clinical use, with the hope that several of these prognostic or predictive markers will guide precision medicine for prostate cancer patients in the near future.
我们对去势抵抗性前列腺癌发病机制认识的进展推动了几种新药的研发,包括雄激素受体导向疗法和化疗。转移性前列腺癌激素治疗开始时联合多西他赛治疗,其总生存期比单纯激素治疗更长。明确这些疗法的合适治疗顺序对于使去势敏感性和去势抵抗性前列腺癌患者获得最大临床获益至关重要。先进的高通量“组学”技术的发展使得能够使用新型标志物来指导该疾病的预后和治疗。在本综述中,我们概述了前列腺癌的基因组格局、去势抵抗性进展的分子机制,以及这些如何影响新药研发及其对选择治疗顺序的临床意义。我们还讨论了许多可能很快进入临床应用的潜在组织或液体生物标志物,希望其中一些预后或预测标志物在不久的将来能指导前列腺癌患者的精准医疗。