Lewis C. Cantley

Lewis Cantley is the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and one of the most influential biochemists and cancer biologists of his generation. He is best known for discovering phosphatidylinositol 3-kinase (PI3K) — an enzyme that is mutated, amplified, or aberrantly activated in approximately one-third of all human cancers and is the central node of the most commonly dysregulated signaling pathway in cancer. In 1984, Cantley's laboratory discovered that the viral oncogene v-src associated with a lipid kinase activity capable of phosphorylating the inositol ring of phosphatidylinositol. Over the following decade, his group purified and characterized this activity as PI3K, cloned its catalytic and regulatory subunits (p110 and p85/p101), and demonstrated that growth factor receptors (such as insulin receptor, PDGFR, and PI3K-activating mutations) signal through PI3K to generate phosphatidylinositol-3,4,5-trisphosphate (PIP3) — a lipid second messenger that recruits and activates AKT and mTOR. This discovery established the PI3K-AKT-mTOR axis as a central regulator of cell growth, survival, and metabolism. Cantley's laboratory subsequently identified PTEN — the phosphatase that degrades PIP3 — as the most commonly deleted tumor suppressor gene in human cancer (after p53), cementing the PI3K pathway's central role in oncogenesis. He also pioneered the development of PI3K-selective inhibitors, working with pharmaceutical partners to develop idelalisib (the first FDA-approved PI3K inhibitor, for blood cancers) and alpelisib (first PIK3CA inhibitor approved for PIK3CA-mutated breast cancer), bringing decades of basic PI3K research to clinical impact. More recently, Cantley's laboratory has explored how insulin and IGF-1 signaling through PI3K connects cancer metabolism to systemic metabolism and diet. He has championed research on ketogenic diets and glucose reduction strategies as potential adjunctive cancer therapies, demonstrating in mouse models that hyperinsulinemia exacerbates PI3K-driven tumor growth — with implications for cancer prevention and metabolic modulation.

Lewis Cantley 是威尔康奈尔医学院Sandra和Edward Meyer癌症中心的Meyer主任，以发现磷脂酰肌醇3-激酶（PI3K）而闻名——这一酶在大约三分之一的人类癌症中发生突变、扩增或异常激活，是癌症中最常见失调信号通路的核心节点。 Cantley 的实验室克隆了PI3K的催化亚基和调节亚基，证明PI3K生成的PIP3可激活AKT和mTOR，建立了PI3K-AKT-mTOR轴作为细胞生长、存活和代谢的中枢调控因子。他还鉴定了PTEN为PIP3的磷酸酶，将其确立为人类癌症中（仅次于p53）最常被删除的肿瘤抑制基因。他领导开发了idelalisib和alpelisib——首批获FDA批准的PI3K抑制剂。