Taplin Mary-Ellen
Harvard Medical School, Dana-Farber Cancer Institute, Lank Center for Genitourinary Oncology, 44 Binney Street, Boston, MA 02115, USA.
Expert Rev Anticancer Ther. 2008 Sep;8(9):1495-508. doi: 10.1586/14737140.8.9.1495.
Androgen receptor (AR) signaling is necessary for the development of prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer was described over 50 years ago and ADT remains the mainstay of systemic therapy. AR signaling remains intact as the disease evolves to castration-resistant prostate cancer (CRPC). Through cellular adaptations, CRPC continues to rely on androgens and AR growth signaling, and thus AR remains an important therapeutic target. CRPC cells upregulate enzymes used in androgen synthesis, thus providing an intracellular source of androgen despite systemic castration. Compounds in development, such as antiandrogens, lyase inhibitors, heat-shock protein-90 inhibitors, histone deacetylase inhibitors and others, will provide new tools to more effectively reduce ligand, inhibit AR and/or inhibit costimulatory pathways and result in improved clinical outcomes.
雄激素受体（AR）信号传导对于前列腺癌的发展至关重要。前列腺癌的雄激素剥夺疗法（ADT）在50多年前就已被描述，并且ADT仍然是全身治疗的主要手段。随着疾病发展为去势抵抗性前列腺癌（CRPC），AR信号传导仍保持完整。通过细胞适应性变化，CRPC继续依赖雄激素和AR生长信号传导，因此AR仍然是一个重要的治疗靶点。CRPC细胞上调雄激素合成中使用的酶，因此尽管进行了全身去势，仍能提供细胞内雄激素来源。正在研发的化合物，如抗雄激素、裂解酶抑制剂、热休克蛋白90抑制剂、组蛋白脱乙酰酶抑制剂等，将提供新的工具，以更有效地减少配体、抑制AR和/或抑制共刺激途径，并改善临床结果。
