José Baselga, MD

2008-2009 BCRF Project:
New molecular-based therapies such as monoclonal antibodies against the HER2 receptor have markedly improved the survival of patients with breast cancer. Despite the benefit of anti-HER2 agents, not all patients with HER2 overexpressing tumors respond to anti-HER2 therapies, and even those patients who initially benefit will eventually develop resistance that will leads to tumor re-growth. This project is directed at identifying the mechanisms of resistance to these agents that will result in novel therapy strategies to revert the resistance problem.

Mid-year Progress Report:
Since October, Dr. Baselga and colleagues have shown promising progress in the characterization of the trastuzumab and lapatinib resistant cells isolated during the last two years. By single nucleotide polymorphisms (SNPs) analysis, they identified 2 loci (19q1 and 14q2) displaying copy number variations in trastuzumab resistant cell lines. They are presently determining if some of the genes present in these regions of the genome are directly responsible for trastuzumab resistance in vitro and in vivo. Together with the identification of novel possible mechanisms of resistance to anti-HER2 therapy the scientists focused on studying different strategies to overcome such resistance.

They demonstrated that dual inhibition of PIK3CA and mTOR catalytic activities with NVP-BEZ235 effectively inhibit both trastuzumab and lapatinib resistant cells. Furthermore, they found that the inhibition of Hsp90 with IPI-504 was equally effective in slowing down the proliferation and tumor growth of both parental and resistant cells. A third major component of this research was set to explore mechanisms of resistance to several novel PI3K inhibitors, which have been identified as capable of rescuing trastuzumab and lapatinib resistance. The Baselga team aims to identify genes involved in PI3K resistance using several approaches, such as cDNA library overexpression and shRNA library screening. They are currently setting up the conditions to perform these experiments.

Bio:
José Baselga is the Chairman of the Medical Oncology Service and Director of the Division of Medical Oncology, Hematology, and Radiation Oncology at the Vall d'Hebron University Hospital in Barcelona, Spain, and a Professor of Medicine at the Universidad Autonoma de Barcelona. He is a member of the Editorial Board for Cancer Cell, Clinical Cancer Research and Investigational New Drugs. Dr. Baselga has published over 150 peer-reviewed articles, in addition to over 300 abstracts and book chapters. His research interests are in clinical breast cancer and in translational and early clinical research in the area of growth factor receptors and downstream molecules as targets for breast cancer therapy. He has been involved in the clinical development of several new agents including: trastuzumab, cetuximab, gefitinib, erlotinib, EMD 72000, ras farnesyltransferase inhibitors, m-TOR inhibitors, and a variety of antiangiogenic agents.

He is a member of several Committees of the American Association for Cancer Research (AACR); Scientific Chairman of the Spanish Breast Cancer cooperative group (SOLTI); past-member of the Board of Directors of the American Society of Clinical Oncology (ASCO); Member of the Scientific Advisory Committee since 2006 and Chairman of the European Society of Medical Oncology (ESMO) and Young Medical Oncologists Working Group; Member of the Scientific Advisory Committee of the Ludwing Institute for Cancer Research (LICR). In addition, Dr. Baselga is currently the President-Elect of ESMO.

Dr. Baselga received his M.D. degree from the Universidad Autonoma of Barcelona in 1982. He performed Internal Medicine Residencies at Vall d'Hebron University Hospital in Barcelona and at State University of New York and a fellowship in Medical Oncology at Memorial Sloan-Kettering Cancer Center in New York. At the completion of his fellowship, he joined the staff at the Breast Medicine service, Memorial Sloan-Kettering Cancer Center until 1996 when he returned to Spain.