Craig B. Thompson

Craig Thompson is one of the most transformative figures in cancer metabolism research and was President and CEO of Memorial Sloan Kettering Cancer Center from 2010 to 2023. He is recognized worldwide for reviving and mechanistically explaining the Warburg effect — the century-old observation that cancer cells preferentially use aerobic glycolysis for energy production even in the presence of oxygen — and for discovering IDH1/2 mutations as cancer drivers through altered metabolite production. Thompson's scientific career began with fundamental studies of lymphocyte activation and survival signaling. Working on IL-3-mediated cell survival, his laboratory discovered that growth factor signals are required not only to promote cell proliferation but also to prevent apoptosis — and that cells deprived of growth factors actively self-destruct rather than becoming quiescent. This demonstrated that cellular survival and metabolic activity are actively coupled to extracellular signaling, a principle that proved foundational for understanding cancer cell metabolism. His critical contribution to cancer metabolism came from the observation that oncogenic signaling (particularly PI3K-AKT-mTOR activation) drives a fundamental reprogramming of cellular metabolism toward anabolic growth — increasing glucose uptake (the Warburg effect), enhancing glutamine consumption, and redirecting carbon flux toward biosynthetic precursors for nucleotides, lipids, and proteins needed by rapidly dividing cells. Thompson demonstrated that the Warburg effect is not merely a consequence of cancer but an active driver of proliferation that provides biosynthetic precursors beyond ATP. Thompson co-founded Agios Pharmaceuticals to translate his IDH mutation research into clinical medicine. In 2009, his laboratory and colleagues discovered that recurrent point mutations in IDH1 (R132H) and IDH2 (R172K) in gliomas and AML produce the oncometabolite 2-hydroxyglutarate (2-HG). 2-HG inhibits α-ketoglutarate-dependent dioxygenases including TET enzymes and histone demethylases, causing widespread epigenetic reprogramming and blocking differentiation. This discovery defined oncometabolites as a new class of cancer drivers and led directly to FDA-approved IDH inhibitors (ivosidenib, enasidenib) for AML.

Craig Thompson 是癌症代谢研究领域最具变革性的人物之一，曾任纪念斯隆凯特琳癌症中心总裁兼首席执行官。他以机制上解释瓦博格效应以及发现IDH1/2突变作为癌症驱动因子而闻名于世。 Thompson 的研究证明，致癌信号通路（特别是PI3K-AKT-mTOR激活）驱动细胞代谢向合成代谢重编程，增加葡萄糖摄取并将碳通量转向快速分裂细胞所需的生物合成前体。他共同创立了Agios制药公司，将IDH突变研究转化为临床医学——2009年他的实验室发现IDH1/2突变产生肿瘤代谢物2-羟基戊二酸，导致表观遗传重编程，直接推动了FDA批准的IDH抑制剂的开发。