James L. Mohler

James Mohler is one of the most distinguished urologic oncologists in the United States, serving as Associate Director for Translational Research at Roswell Park Comprehensive Cancer Center, where he has spent the majority of his career. He is best known for two major contributions: his seminal work demonstrating that castration-resistant prostate cancer synthesizes androgens de novo within the tumor itself — providing the mechanistic foundation for the development of abiraterone — and his decades of service developing and updating the NCCN Clinical Practice Guidelines for Prostate Cancer, which are the most widely adopted prostate cancer management guidelines globally. Mohler's laboratory demonstrated that CRPC tumors maintain high intratumoral androgen concentrations despite castrate serum levels, and that these tumors express the complete enzymatic machinery (including CYP17A1) for de novo androgen synthesis from cholesterol and adrenal precursors. This work directly explained the clinical success of abiraterone, a CYP17A1 inhibitor targeting both adrenal and intratumoral androgen production, and provided a mechanistic rationale for the failure of conventional androgen deprivation to eliminate AR signaling in advanced disease. As Chair of the NCCN Prostate Cancer Guidelines Panel for many years, Mohler oversaw the annual updates of guidelines used by oncologists, urologists, and radiation oncologists worldwide. These guidelines synthesize evidence on screening, diagnosis, staging, active surveillance, surgery, radiation, hormonal therapy, chemotherapy, immunotherapy, and supportive care — shaping the treatment of hundreds of thousands of patients annually. His contributions to guideline development represent one of the most direct and broad impacts on prostate cancer practice in modern medicine.

James Mohler 是美国最杰出的泌尿肿瘤学家之一，在罗斯威尔帕克综合癌症中心担任转化研究副主任。他最著名的贡献是：证明去势抵抗性前列腺癌在肿瘤内自身合成雄激素（为阿比特龙的研发奠定机制基础），以及数十年来主持制定和更新全球最广泛采用的 NCCN 前列腺癌临床实践指南。 Mohler 实验室证明了尽管血清雄激素水平在去势状态下很低，CRPC 肿瘤仍维持高水平的肿瘤内雄激素浓度，并表达完整的从胆固醇和肾上腺前体开始进行新型雄激素合成的酶系统。这项工作直接解释了阿比特龙的临床成功，并为传统雄激素剥夺疗法不能消除晚期疾病中 AR 信号的失败提供了机制依据。