2005 - Lewis Cantley

Harvard Medical School
Chief, Division of Signal Transduction
Beth Israel Deaconess Medical Center, Boston, MA

Motivation:
The 2005 Pezcoller Foundation-AACR International Award for Cancer Research is given to Lewis C. Cantley, PhD for his outstanding contributions to the field of signal transduction, including his discovery of phosphoinositide 3-kinase and the elucidation of its role in signal transduction, as well as for his establishment of methods for unbiased determination of protein-protein interactions and kinase specificity.
Early in his independent career, Dr. Cantley identified a novel enzyme activity associated with activated growth factor receptors and oncoproteins. It began with his collaborative research with Ray Erickson, when they identified a lipid kinase activity associated with immunoprecipitates of the v-Src oncoprotein. The seminal step that Dr. Cantley took was to show that this enzyme could phosphorylate the 3-hydroxyl of phosphatidylinositol and its derivatives, which is now termed phosphoinositide 3-kinase (PI3K). Dr. Cantley speculated that the novel lipids also possessed an intrinsic signaling function. PI3K activation is now recognized as a centrally important step in mitogenic and oncogenic signaling. Dr. Cantley has continued to lead the field, contributing to the molecular characterization of PI3K and related phosphoinositide kinases, identifying PI3K effector proteins that bind the lipids, and determining the phenotypes of mice lacking specific PI3K effector proteins that bind the lipids, and determining the phenotypes of mice lacking specific PI3K isoforms. The impact of Dr. Cantley’s contributions to cancer are profound. In addition to opening up a key regulatory pathway of oncogenesis that is manifested in many, if not most human malignancies, his contributions also provide opportunities for drug targeting of PI3K or downstream effectors. Indeed, many such drugs are in clinical trials for cancer.
In addition to his seminal work with PI3K and related effector molecules, Dr. Cantley initiated a new line of research aimed at unbiased determination of molecular specificity of protein interaction domains using oriented peptide libraries. Beginning with nonenzymatic modules such as the Src-homology-2 (SH2) domain, this work has expanded to examine the substrate specificity of protein kinases. This work has had a truly extraordinary impact on the field of signal transduction. Importantly, Dr. Cantley and colleagues have developed a Website, called Scansite, in which users can input protein sequences and rapidly determine likely sites of phosphorylation by an array of kinases, and likely motifs for direct interaction with modular domains of other specific proteins. Thus, through the innovations of Dr. Cantley, molecular interactions in signal transduction can now be identified or predicted with much greater speed and precision. In his own laboratory, Dr. Cantley has applied these approaches to the delineation of numerous signaling pathways of relevance to cancer.
Dr. Cantley obtained a B.S. from Wesleyan College and a PhD from Cornell University. He completed postdoctoral training at Harvard and joined the Department of Biochemistry and Molecular Biology in 1978 as an Assistant Professor. Dr. Cantley then held a professorship at Tufts University School of Medicine from 1985 to 1992, when he returned to Harvard Medical School. Dr. Cantley is currently a Professor of Systems Biology at Harvard Medical School and Chief of the Division of Signal Transduction at Beth Israel Deaconess Medical Center. He is an elected member of the American Academy of Arts and Sciences and to the National Academy of Sciences. Among his awards are the ASBMB Avanti Award for Lipid Research, the Heinrich Weiland Preis for Lipid Research, and the Caledonian Prize from the Royal Society of Edinburgh.