Pezcoller Foundation-AACR International Award for Cancer Research

04/04/05

Lewis C. Cantley honored for groundbreaking work in signal transduction

PHILADELPHIA -- Lewis C. Cantley, Ph.D., professor of Systems Biology at Harvard Medical School and chief of the Division of Signal Transduction at Beth Israel Deaconess Medical Center, both in Boston, is the recipient of the eighth annual Pezcoller Foundation-American Association for Cancer Research International Award for Cancer Research, for his leadership in the field of signal transduction, including the discovery of phosphoinositide 3-kinase (PI3K).

The annual award, established in 1997, recognizes an individual who has made a major scientific discovery in basic or translational cancer research.

Cantley will give an award lecture at the 96th AACR Annual Meeting in Anaheim, Calif., April 16-20, 2005. His talk, entitled "The Role of PI3K in Cancer," will be at 11:30 a.m., Sunday, April 17, in Hall A of the Anaheim Convention Center. In honor of Cantley, the Pezcoller Foundation will hold an award ceremony later in the spring, at its location in Trento, Italy. Cantley will receive a cash prize of 75,000 and a medallion.

"Dr. Cantley's contributions to cancer are profound," said AACR Chief Executive Officer Margaret Foti, Ph.D., M.D. (h.c.). "In addition to opening up a key regulatory pathway of oncogenesis that is manifested in many, if not most human malignancies, they also provide opportunities for drug targeting of PI3K or downstream effectors.

"Indeed, many such drugs are in clinical trials for cancer and are expected to also find use in treatment of inflammatory and allergic diseases."

As a graduate student at Cornell University, Cantley studied changes in proteins made by rearranging molecules spatially without breaking the covalent bonds, known as conformational changes. The work stemmed from his early interest in the biochemical basis for cell regulation of metabolism. Conformational changes are an important aspect of enzyme regulation. This background provided Cantley with insight into the biochemical, structural and dynamic bases for protein interactions that control cellular processes.

Cantley continued to focus on the biochemical basis for the mechanism and regulation of membrane-associated enzymes as an assistant professor in the biochemistry and molecular biology department at Harvard University.

From there, Cantley joined the physiology faculty of Tufts University School of Medicine where, with colleagues, he examined the biochemical mechanisms of cellular response to oncogenes and growth factors. It was during this time that his laboratory discovered phosphoinositide 3-kinase (PI3K), an enzyme that puts a phosphate group on the membrane lipid phosphatidylinositol. Although prior work in the 1950s had shown that phosphatidylinositol was phosphorylated in human tissues, Cantley's laboratory discovered an enzyme that could phosphorylate a unique position on phosphatidylinositol (the 3 position of the inositol moiety), revealing a new lipid not previously known to exist in nature. More importantly, this lipid was produced only when cells were stimulated with growth factors or made cancerous with oncogenes. In addition, genetic evidence indicated that activation of PI3K by oncogenes was a critical event in transforming a normal cell to a cancerous cell.

In 1992, Cantley moved to Harvard Medical School and Beth Israel Deaconess Hospital, where he and his team further explored the PI3K pathway. They postulated that the novel membrane lipid made by PI3K might act as an intracellular "messenger" by recruiting to the cell membrane the machinery (signaling proteins) needed to communicate a growth signal to the cell. Continuous activation of PI3K would allow the cell to continually grow and make copies of itself, resulting in a cancerous tumor. Research over the past decade by numerous laboratories has supported this model and provided evidence that PI3K plays a critical role in many human cancers.

In addition, research from Cantley's laboratory and others has revealed that PI3K also is a significant factor in insulin signaling and in immune cell signaling. As a result, pharmaceutical intervention in the PI3K pathway is being explored in a variety of diseases, including cancer, diabetes and immune diseases.

"I am honored to have received this award indicating an international recognition of the importance of PI 3-kinase in human cancer," Cantley said.

"Over the past 20 years, our understanding of PI 3-kinase has progressed from an unusual lipid kinase activity that we found associated with oncogene products to the central player in a network that controls the growth and survival of cancer cells. There is now much optimism that the elucidation of this network is revealing effective targets for pharmaceutical intervention in a wide variety of human cancers."

A summa cum laude graduate of West Virginia Wesleyan College, Cantley obtained a Ph.D. in Biophysical Chemistry from Cornell University in 1975. He did postdoctoral research at Harvard from 1975 till 1978 and joined the Department of Biochemistry and Molecular Biology as an assistant professor in 1978. He is a member of the American Academy of Arts and Sciences and the National Academy of Sciences, and serves on the editorial boards of the journals Cell and the Journal of Cell Biology. A series of awards is given annually by the AACR the world's oldest and largest professional society representing cancer scientists from the United States and more than 60 other countries to recognize world-class accomplishments in basic research, clinical care, therapeutics and prevention.

Source: Eurekalert & others

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