Medical Director of Evelyn H. Lauder Breast Center Memorial Sloan Kettering Cancer Center New York, New York BCRF Scientific Director
In addition to serving as BCRF’s Scientific Director, Dr. Norton is also involved in collaborations with BCRF granteets, Rachel Hazan, Taha Merghoub and Jedd Wolchok. Dr. Hazan’s team is working on strategies to prevent drug resistanc in HER2+ breast cancer by identifying new targets for combination therapies. Approximately 25% of breast cancers overexpress HER2, a protein found on the surface of tumor cells that is known to promote tumor growth. Targeted therapies against HER2-positive breast cancer, including traztuzumab and lapatinib, have been successful in stopping the growth of many, but not all of these tumors. Currently, there are no clinically validated markers of resistance to HER2 therapy. Dr. Hazan and her team recently discovered high levels of another growth-promoting protein called Fibroblast Growth Factor Receptor 4 (FGFR4) in HER2+ breast cancer cells and tumors. They believe that the two proteins might work together in driving an aggressive disease that is resistant to HER2-directed therapies such as trastuzumab. In their 2014-2015 BCRF study, Drs. Hazan and Norton will test whether neutralizing FGFR4 will re-sensitize tumors to HER2-based therapy in laboratory models of breast cancer to determine if combined therapy of FGFR4 and HER2 drugs might benefit those patients with advanced HER2+ breast cancer. Furthermore, the researchers believe that FGFR4 expression in HER2+ breast cancers might serve as a marker of resistance to targeted therapy and will work in collaboration with Dr. Joseph Sparano to evaluate whether this is the case.
Immnotherapy has re-emerged as a potential strategy for the treatment of breast cancer. Effective immunization against breast cancer is difficult, however because breast cancer arises from cells that were once normal and the body has elaborate controls to stop the immune system from attacking “host” tissues. However, research by Drs. Merghoub, Norton and Wolchok has revealed a way to trick the immune system by using a vaccine from a different species. It works because the immune system recognizes the vaccine as "foreign" and generates an immune response to destroy breast cancer cells as if they were foreign invaders. This research has moved from the laboratory to patients and in the last year, the researchers completed a clinical trial to test the safety and feasibility of the vaccine against breast cancer. In addition to these studies, the research team is pursuing other strategies to improve tumor response to immunotherapy including radiation therapy, which has been shown to activate the immune system, and several targeted combination approaches. The investigators are also collaborating with Dr. Heather McArthur, to test the effects of immunotherapy in combination with cryoablation, a technique that uses freezing temperatures to kill tumor cells and activate a local immune response in patients with early stage breast cancer. Collectively, these studies will have a significant impact on advancing immunotherapy, which has been successful for the treatment of metastatic melanoma, to improve breast cancer outcomes.
Dr. Larry Norton is Medical Director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center. He is a founder of The Breast Cancer Research Foundation and has served as its Scientific Director since the Foundation's inception in 1993.
Dr. Norton is the founding incumbent of the Norna S. Sarofim Chair of Clinical Oncology at MSKCC and a Professor of Medicine in the Weill Cornell Medical College. He received his AB with Highest Distinction from the University of Rochester and his MD from the College of Physicians and Surgeons of Columbia University. He trained in medicine and medical research at the Albert Einstein College of Medicine and the National Cancer Institute (NCI).
Dr. Norton has dedicated his life to the eradication of cancer by activities in medical care, laboratory and clinical research, advocacy, and government. He was a U.S. Presidential appointee to the National Cancer Advisory Board (the board of directors of the NCI) serving as Chair of the Budget Sub-Committee. A former Director of the American Society of Clinical Oncology, he served as President of ASCO and subsequently Chair of the ASCO Foundation. He has been Vice-Chair of the Lymphoma Committee and a long-serving Chair of the Breast Committee of the Cancer and Leukemia Group B (now the Alliance for Clinical Trials in Oncology). He has served on or chaired numerous committees of the National Cancer Institute, National Institutes of Health, and the Institute of Medicine of the National Academy of Sciences. He is an editorial board member or reviewer for numerous medical journals and on the advisory boards of many advocacy and medical institutions including the Cold Spring Harbor Laboratory Cancer Center and several Specialized Programs of Research Excellence.
Dr. Norton's personal research has focused on the use of medicines to treat cancer, particularly the application of mathematical methods to optimizing dose and schedule. He has been involved in the development of several effective agents including paclitaxel and trastuzumab. He co-invented the Norton-Simon Model of cancer growth, which has broadly influenced cancer therapy, and more recently the self-seeding concept of cancer metastasis and growth. He is the Principal Investigator of an NCI Program Project Grant in Models of Human Breast Cancer and an author of more than 350 published articles and many book chapters.
For his work Dr. Norton has received many honors including election to Phi Beta Kappa and Alpha Omega Alpha and recognition from the MD Anderson Cancer Center, the Society for MSKCC, the Italian-American Foundation for Cancer Research, the Don Shula Foundation, SHARE (NY), the Susan G. Komen Foundation, and The Breast Cancer Research Foundation. He received ASCO's highest honor, the David A. Karnofsky Award, in 2004, and was a McGuire Lecturer at the San Antonio Breast Cancer Symposium. He has served as a visiting professor throughout the U.S., Canada, South America, Europe, Israel, and Asia and has trained many cancer physicians and researchers. In 2010, Dr. Norton was one of three individuals honored for clinical excellence and presented with a National Physician of the Year Award by Castle Connolly Medical Ltd. Honorees for this award are selected based on an extensive process involving thousands of nominations by physicians listed in Castle Connolly's America's Top Doctors and America's Top Doctors for Cancer guides. More recently, Dr. Norton received the 2013 Gianni Bonadonna Award from ASCO, in recognition of his distinguished record of accomplishments in advancing the field of breast cancer.