Yale’s picks to beat cancer: a pair of aces

It has been an eventful December for the advancement of basic and translational cancer research at Yale. On the 13th, Yale University announced that Joseph Schlessinger, Ph.D., a world-renowned scientist with an unparalleled track record of identifying molecular targets for novel anticancer drugs, was named the first director of the University’s new Cancer Biology Institute (CBI), one of five major interdisciplinary research initiatives located on Yale’s West Campus.

Just a week before, Thomas J. Lynch Jr., M.D., director of Yale Cancer Center (YCC), broke the news that YCC has appointed Roy S. Herbst, M.D., Ph.D., who has also had a distinguished career in the development of new cancer therapies, as chief of medical oncology at Smilow Cancer Hospital and associate director for translational research.

Schlessinger, whose appointment is effective immediately, will retain his positions as chair and William H. Prusoff Professor of Pharmacology at the School of Medicine, dividing his time between the medical campus and West Campus. Herbst comes to Yale in March 2011 from MD Anderson Cancer Center at the University of Texas in Houston, where he is professor of medicine, chief of the section of thoracic medical oncology, and Barnhart Family Distinguished Professor in Targeted Therapies. His appointment marks Herbst’s return to Yale, where he received his undergraduate and master’s degrees.

“Dr. Schlessinger has significantly expanded the footprint and faculty roster of the Department of Pharmacology, which was ranked in the top three departments this year by the National Research Council,” says Robert J. Alpern, M.D., dean of the School of Medicine. “His taste for excellence has resulted in outstanding faculty recruitments, and we look forward to the application of his talents in building an outstanding Cancer Biology Institute.”

Under Schlessinger’s direction, the CBI plans to hire 150 research scientists, including 11 principal investigators, over the next three to four years, with the primary goal of pinpointing root molecular causes of cancer, identifying new molecular targets, and developing new drug treatments.

These researchers will work in concert with scientists at the neighboring Yale Center for Genome Analysis, using state-of-the-art genomic sequencing techniques to better understand and exploit the molecular profiles of various tumor types.

The institute will significantly increase the extent of basic research on cancer at Yale, especially in the areas of computational biology, cancer genomics, cancer immunology, and drug discovery, and it will complement Yale’s translational and clinical research programs, including a major expansion of clinical trials planned by YCC.

Schlessinger, known to colleagues and friends as “Yossi,” is a pioneer in the field of signal transduction, the means by which receptors in the cell membrane, when bound to certain molecules, pass signals to the interior of the cell that guide basic processes such as cell division and cell growth.

In particular, over several decades, his group has done fundamental research on signaling by receptor tyrosine kinases (RTKs), a set of related cell-surface proteins that affect cell proliferation, differentiation, and survival. Certain mutations in RTKs can result in faulty signaling, which in turn can cause aberrant cell proliferation that may ultimately lead to cancer.

Blocking RTK activation has become a major strategy in anticancer drug design. Schlessinger and colleagues have formed three companies—Sugen Inc. in 1991, Plexxikon in 2001, and Kolltan in 2008—and drugs based on insights gained in his laboratory are having a major impact in the lives of patients with liver, kidney, stomach, and skin cancers.

Sugen’s drug Sutent, approved by the FDA in 2006 for kidney and stomach cancers, was one of the first in a new generation of targeted cancer drugs. An experimental compound, PLX4032, which was discovered by Plexxikon and is currently in clinical development in partnership with Roche, has attracted wide media coverage for its unprecedented success in early-stage clinical trials for the treatment of melanoma. The drug is now in Phase III trials for melanoma, and is also in Phase I trials for the treatment of colorectal cancer.

Schlessinger, who was recruited to Yale in 2001, was born in Croatia and educated at Hebrew University and the Weizmann Institute of Science in Israel. He was a member of the Weizmann Institute from 1978 to 1991, and moved to New York University School of Medicine in 1990.

He is a member of the National Academy of Sciences and the Institute of Medicine and serves on the editorial boards of numerous journals, includingCell and Molecular Cell. He received the Taylor Prize in 2000, the Dan David Prize in 2006, and the Pezcoller Prize from the American Association for Cancer Research (AACR) in 2010.

Drugs that target RTKs have also been of great interest to Herbst, who has spearheaded clinical studies of many such drugs over the last several years. His work using erlotinib (Tarceva) in combination with bevacizumab (Avastin) was among the first to combine multiple targeted agents for non-small cell lung cancer (NSCLC).

Herbst is co-principal investigator of the Biomarker-Based Approaches of Targeted Therapy for Lung Cancer Elimination Program (BATTLE) Trial, which has significantly advanced “personalized” therapy of NSCLC by using molecular analysis of tissue biopsies to determine the best available targeted treatment for each patient. He recently developed a BATTLE-2 trial to explore novel combinations of agents to target genetically mutated pathways in lung cancer and to overcome drug resistance. Herbst plans to open this study at Yale and to bring this approach to other forms of cancer.

In his new position, Herbst hopes to bring novel and more personalized therapies to cancer treatment to improve efficacy and reduce toxicities. He will work to help integrate Yale’s strengths in basic science and translational medicine to have a more direct impact on clinical care.

“Dr. Herbst is nationally recognized for his leadership and expertise in lung cancer treatment and research,” says YCC Director Lynch, also physician-in-chief of Smilow Cancer Hospital at Yale-New Haven. “He is a natural leader and will have a critical role in building our cancer program while mentoring the next generation of cancer doctors at Yale.”

Herbst is a member of the AACR, for which he is senior editor of Clinical Cancer Research, as well as the American Society of Clinical Oncology and the Institute of Medicine’s National Cancer Policy Forum. He is a fellow of the American College of Physicians. He has authored more than 200 peer-reviewed papers and has current grant funding for his work from numerous sources, including the National Cancer Institute, the AACR, and multiple charitable foundations.

Herbst received his medical degree from Cornell University Medical College and earned a Ph.D. in molecular cell biology from the Rockefeller University. He completed his medical oncology fellowship at Dana-Farber Cancer Institute and a medical hematology fellowship at Brigham and Women’s Hospital in Boston, where he additionally received a master’s degree from Harvard University’s clinical investigator training program.