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José Baselga, MD, PhD
Physician-in-Chief and Chief Medical Officer
Member, Human Oncology and Pathogenesis Program
Physician Attending, Department of Medicine and
Division of Solid Tumor Oncology
Memorial Sloan Kettering Cancer Center
New York, New York
Studies are focused on improving response to targeted therapy and improve outcomes in patients with advanced breast cancer.
Mutations in the PI3KCA gene are being explored as potential biomarkers to predict response to PI3K inhibitors.
These studies may lead to clinical trials testing PI3K inhibitors in a select group of patients that harbor specific mutations in the PIK3CA gene.
Hyperactivation of the PI3K-AKT signaling pathway is a frequent event in cancer and results in cell proliferation and survival. Many inhibitors of this pathway have been developed, some of which are currently in late clinical testing and showing promising results.
One way to identify patients that are more likely to respond to PI3K inhibitors is to analyze the DNA of their tumors and search for mutations in PIK3CA, the gene encoding the PI3K enzyme. However, among patients with PIK3CA-mutant tumors, the response to these drugs is variable, with some patients achieving durable clinical benefit and others being relatively resistant to the therapy.
Dr. Baselga’s group discovered that about 15 percent of PIK3CA-mutated tumors have not just one, but two mutations in the PIK3CA gene.These patients seem to respond better than most patients to PI3K inhibitors.
In the next year, the team will study whether the presence of two different mutations in PIK3CA confers a cell growth advantage compared to single mutations. Tumors with two mutations in PIK3CA may be more dependent on the PI3K pathway for growth and survival, and therefore, may be more susceptible to the antitumor effects of PI3K inhibitors. This work could shed new light on the biology of PI3K and provide the rationale to design clinical trials testing the antitumor activity of PI3K inhibitors specifically in patients with tumors carrying two mutations in PIK3CA.
In addition, Dr. Baselga is part of an MSKCC team including Drs. Sarat Chandarlapaty, Maurizio Scaltriti, and Larry Norton who are working to identify genetic alterations that convert normal breast cells into breast cancer cells and then develop drugs that specifically target those alterations. This project utilizes the latest technologies to characterize how resistance occurs in patients who are receiving targeted therapies. Overall, these studies will provide a testing ground that reproduces the molecular features of the patient’s tumor, mimicking their response to the treatment and allowing for the development of personalized, precision medicine.
Dr. Baselga MD, PhD is the Physician-in-Chief of Memorial Sloan Kettering Cancer Center and has also been named as AACR President for 2015-2016. Dr. Baselga received his MD degree from the Universidad Autonoma of Barcelona in 1982. From 1996 to 2010, he was the Chairman of the Medical Oncology Service and Founding Director of the Vall d’Hebron Institute of Oncology (VHIO) at the Vall d'Hebron University Hospital in Barcelona. From 2010 to 2012, he was the chief of the Division of Hematology/Oncology and associate director of the Massachusetts General Hospital Cancer Center.
Dr. Baselga has received a number of awards including a Young Investigator Award (1992) and a Career Development Award (1994) from ASCO, Elected Member of the American Society of Clinical Investigation (2004), AACR-Rosenthal Family Foundation Award (2008), and King James I Award (2008). In October 2014 he was elected to the Institute of Medicine. He has published over 300 peer-reviewed articles and is the founding editor of Cancer Discovery.
José Baselga is a researcher and clinician focusing primarily on breast cancer. His laboratory focuses on mechanisms that limit the sensitivity to targeted therapy in solid tumors, in particular to PI3K/Akt/mTOR inhibitors and anti-HER2 agents. He has also been involved in the development of several molecularly targeted agents including trastuzumab (Herceptin®) and lapatinib (Tykerb®).