José Baselga, MD

2009-2010 BCRF Project:
(made possible by generous support from The Housewares Charity Foundation)

New molecular-based therapies targeting the HER2 receptor have provided substantial clinical benefit to patients with breast cancer. Despite the benefit, the effectiveness of these agents is limited by either primary or acquired resistance. With funding from BCRF, Dr. Baselga and colleagues have identified novel treatment combinations with either two different types of anti-HER2 agents or the combination of anti-HER2 agents with PI3K inhibitors that are efficacious in the treatment of trastuzumab resistant tumors. This ongoing study appears to increase efficacy of current HER2 therapies.

Over the last year, Dr. Baselga and colleagues have shown promising progress in indentifying novel mechanisms of resistance to the anti-HER2 therapy trastuzumab and PI3K/mTOR inhibitors. One of these findings indicates that treatment of HER2 positive cell lines with dual PI3K/mTOR inhibitors resulted in an upregulation of the MAPK pathway. Interestingly, this unwanted side effect can be overcome by treating the cells with both trastuzumab and PI3K inhibitors, suggesting that the dual inhibition of the PI3K and HER2 pathways may be effective treatment of cancers that escape either treatment alone.

Mid-Year Progress Report:
Dr. Baselga reports that his team has made progress in the characterization of the trastuzumab resistant cells isolated in his laboratory. The researchers had preliminary data that had identified acquired amplification of Cyclin E as a mechanism of resistance to anti-HER2 therapy. Their data has now confirmed this suspicion and they are now carefully analizing cyclin E overexpression in patients who have ceased to respond to trastuzumab (Herceptin). If this is confirmed in patients, it would represent one of the first mechanisms of acquired resistance to trastuzumab and it could be therapeutically exploitable in the clinic. The scientists have also shown that they can revert trastuzumab resistance with novel inhibitors of the PIK3CA/mTOR/Akt pathway and by inhibit progression of cells through the cell cycle. Of particular interest are the possible therapeutic combinations of PI3K and Akt inhibitors with either anti-HER2 agents or MEK inhibitors. These combinations would prevent the activation of the complementary MAPK pathway, induced by PI3K inhibition.

Bio:
José Baselga is the Chairman of the Medical Oncology Service and Director of the recently established Vall d’Hebron Institute of Oncology (VHIO) at the Vall d'Hebron University Hospital in Barcelona, Spain. He is also a Professor of Medicine at the Universidad Autonoma de Barcelona. Dr. Baselga holds the position of Scientific Chairman of SOLTI, the Spanish Breast Cancer Cooperative Group. He is a member of the Editorial Boards of Cancer Cell, Journal of Clinical Oncology, Clinical Cancer Research and Annals of Oncology.

Dr. Baselga has published over 200 peer-reviewed articles, in addition to over 400 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 conducted the initial clinical trials with the monoclonal antibodies cetuximab and trastuzumab. In addition, he has been involved in the clinical development of several new agents including: gefitinib, erlotinib, lapatinib, pertuzumab, m-TOR, PI3K, TGFß, SRC, Insulin-like Growth Factor Receptor Inhibitors and a variety of anti-angiogenic agents. His main focus in the laboratory and in the clinic is the area of novel anti-HER2 agents, in the identification of mechanisms of resistance to anti-HER2 agents and therapeutic approaches to target the PI3K pathway.

Dr. Baselga is currently President of the European Society of Medical Oncology (ESMO). He is a member of several Committees of the American Association for Cancer Research (AACR) and a member of the AACR Research Council and the AACR Board of Directors; a past member of the Board of Directors of the American Society of Clinical Oncology (ASCO), a past member of the Board of Directors of the European Organization of Research on Treatment of Cancer (EORTC); and a member of the Scientific Advisory Committee of the Ludwig Institute for Cancer Research.

Dr. Baselga has received a number of awards including a Young Investigator Award from ASCO (1992), a Career Development Award from ASCO (1994), a Brystol-Myers Squibb Unrestricted Cancer Grant Award (2002-2006), an Honorary Membership Award from The European Society for Therapeutic Radiology and Oncology (ESTRO) (2004); the Waun Ki Hong Visiting Professorship at U.T.M.D. Anderson Cancer Center in Houston, TX (2002); named Distinguished Alumnus from Memorial Sloan Kettering Cancer Center, NY (2004); Elected Member of the American Society of Clinical Investigation (2004); Annual Award from ESMO (2005); American- Italian Cancer Foundation (AICF) Prize for Scientific Excellence in Medicine (2007); AACR-Rosenthal Family Foundation Award (2008); and King James I Award (2008)

Dr. Baselga received his M.D. degree from the Universidad Autonoma of Barcelona in 1982. He did his Internal Medicine Residency at both Vall d’Hebron University Hospital in Barcelona, Spain and the State University of New York in the US. He completed a fellowship in Medical Oncology at Memorial Sloan-Kettering Cancer Center in New York and subsequently stayed on as a faculty member of the Breast Medicine Service at Memorial Sloan-Kettering until 1996 when he returned to Spain.