Charles L. Sawyers

Charles Sawyers is one of the most transformative figures in modern oncology, best known for co-developing enzalutamide (Xtandi), a next-generation androgen receptor (AR) antagonist that has dramatically extended survival in men with castration-resistant prostate cancer (CRPC). His career has been defined by bridging deep molecular insight into oncogenic signaling with direct therapeutic innovation. At Memorial Sloan Kettering, he chairs the Human Oncology and Pathogenesis Program and is an investigator of the Howard Hughes Medical Institute. Sawyers' laboratory established the mechanistic basis for AR pathway reactivation in CRPC — the central paradox that prostate cancer cells continue to rely on AR signaling even after androgen deprivation therapy. His group showed that AR overexpression, activating mutations, and aberrant co-activator recruitment allow tumors to survive at castrate androgen levels. This work directly motivated the development of more potent AR antagonists. Collaborating with Michael Jung at UCLA, his team designed enzalutamide to bind AR with greater affinity and prevent its nuclear translocation, ultimately winning FDA approval in 2012 for post-chemotherapy CRPC and later for earlier disease stages. Beyond prostate cancer, Sawyers made foundational contributions to BCR-ABL biology in chronic myelogenous leukemia, working with Brian Druker on imatinib resistance mechanisms and the development of second-generation inhibitors. His dual track record across two major malignancies makes him one of the most influential translational oncologists of his generation, and his work exemplifies the pathway from molecular mechanism to approved therapy.

Charles Sawyers 是现代肿瘤学最具变革性的人物之一，因共同开发恩扎鲁胺（Xtandi）而闻名。恩扎鲁胺是一种新一代雄激素受体（AR）拮抗剂，已显著延长去势抵抗性前列腺癌（CRPC）患者的生存期。他在纪念斯隆凯特琳癌症中心担任人类肿瘤学与发病机制项目主任，并担任霍华德·休斯医学研究所研究员。 Sawyers 实验室阐明了 CRPC 中 AR 通路再激活的机制基础——即前列腺癌细胞在雄激素剥夺治疗后仍依赖 AR 信号传导的核心悖论。他的团队证明了 AR 过表达、激活性突变和异常共激活剂招募使肿瘤在去势雄激素水平下得以存活，这直接推动了更强效 AR 拮抗剂的开发，最终于2012年获得 FDA 批准用于化疗后 CRPC 的治疗。