José Baselga is a Spanish medical oncologist and researcher focused on the development of novel molecular targeted agents, with a special emphasis in breast cancer. Baselga serves as Physician-in-Chief at the Memorial Sloan Kettering Cancer Center.
Video José Baselga
Education and career
Baselga received his MD and PhD degrees from the Autonomous University of Barcelona in 1982. 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.
From 1996 to 2010, Baselga was the Chairman of the Medical Oncology Service and Founding Director of the recently established 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 MGH Cancer Center in Massachusetts.
He is one of the principal investigators of the Stand Up to Cancer "Dream Team" for "Targeting the PI3K Pathway in Women's Cancers". He has been involved in the development of several targeted drugs for cancer including cetuximab, pertuzumab, trastuzumab and lapatinib.
He was appointed Physician-in-chief at MSK in 2012 and was appointed a professor of medicine at Weill Cornell Medical College in 2013.
Maps José Baselga
Scientific accomplishments
Baselga's investigative focus is translational cancer research. He has devoted much of his effort to developing molecularly targeted treatments for breast cancer and identifying mechanisms of resistance to cancer therapies. Baselga has advanced the clinical use of several monoclonal antibody and pharmacologic therapies to treat breast and other cancers, and has substantial experience leading clinical trials. He holds patents related to cancer diagnostic methods, antibody reagents, and therapeutic approaches.
Anti-EGFR Treatments for Cancer
As a research fellow at MSK, Baselga worked under the mentorship of John Mendelsohn, who, with others, is credited with developing cetuximab, a monoclonal antibody against the epidermal growth factor receptor (EGFR). Baselga was instrumental in establishing the clinical efficacy of EGFR-inhibitors as anti-cancer therapy, a continuing research interest of his.
HER2-positive breast cancer
Around the same time that he began the anti-EGFR studies, Baselga became interested in HER2-positive breast cancers. In his early work, Baselga discovered a synergistic therapeutic effect between paclitaxel and trastuzumab, a monoclonal antibody therapy (Herceptin), which is directed against the HER2 receptor. The discovery resulted in clinical trials of this combination therapy to treat HER2-positive breast cancer.
Over time, some patients become resistant to trastuzumab, prompting the need for further studies to understand drivers of this process. Knowing this, the Baselga laboratory contributed to the identification of a number of molecular pathways leading to resistance to trastuzumab and other anti-HER2 agents).
Some of them, including the presence of a truncated HER2 receptor (p95HER2) and hyper-activation of the PI3K-Akt-mTOR pathway, have been clinically validated and are therapeutically exploitable.
Baselga has also led other worldwide clinical trials with anti-HER2 agents, including studies in neo-adjuvant and adjuvant settings. As one example, he led the phase II and III clinical development of pertuzumab, a novel anti-HER2 antibody that has a complementary mechanism of action with trastuzumab. In this study, pertuzumab combined with trastuzumab improved the disease-free survival and the overall survival in the first-line setting; pertuzumab added to adjuvant trastuzumab plus chemotherapy has also been shown to improve rates of invasive-disease-free survival in early breast cancer.
He also was the principal investigator of the neoadjuvant study that demonstrated that the combination of trastuzumab and the kinase inhibitor lapatinib was significantly superior to either single agent alone in leading to pathological disappearance of the disease.
PI3K Pathway Inhibitors
To complement the EGFR-inhibitor and HER2-inhibitor work, Baselga's focus has shifted to include investigations of the phosphoinositide 3-kinase (PI3K) pathway in breast cancer, and mechanisms of resistance to mammalian target of rapamycin (mTOR) and PI3K pathway inhibitors. Among other findings, his group observed that inhibition of mTOR or PI3K induced intra-tumoral activation of compensatory feedback loops that resulted in activation of multiple pathways including insulin, estrogen, and MEK kinase pathways.
Baselga also led several clinical trials testing the combination of PI3K inhibitors with agents blocking these compensatory pathways in patients with breast cancer harboring PI3K mutations. In a seminal paper, Baselga's lab reported unprecedented clinical activity of combination therapy using the mTOR inhibitor everolimus with the anti-estrogen agent examestane in metastatic estrogen receptor-positive breast cancer. He also discovered that tumors that are refractory to anti-HER2 therapy, but have mutations in PIK3CA, the gene coding for the catalytic subunit of PI3K, are exquisitely sensitive to specific inhibitors targeting this subunit.
In the laboratory, he has uncovered several routes to acquired resistance to HER2, mTOR, and PI3K inhibitors, all validated in the clinical setting. Baselga has led several clinical trials of combination therapy with some of these agents to determine the optimal first-line therapy for patients with triple-negative breast cancer, a particularly aggressive form of breast cancer.
Honors and awards
- Young Investigator Award, American Society of Clinical Oncology (ASCO) (1992-1993)
- Career Development Award, American Society of Clinical Oncology (ASCO) (1994-1997)
- Elected Member, American Society of Clinical Investigation (2004)
- American Italian Cancer Foundation Prize for Scientific Excellence in Medicine (2007)
- American Association for Cancer Research-Rosenthal Family Foundation Award (2008)
- King Jaime I Award in Medical Research, Valencia, Spain (2008)
- Gold Medal, Queen Sofia Spanish Institute, NY (2010)
- Joseph B. Martin Award, Massachusetts General Hospital, Boston, MA (2012)
- Elected Member, National Academy of Medicine (2014)
- John Wayne Clinical Research Lecture Award, Society of Surgical Oncology (2016)
- XXVIII Catalonia International Prize (2016)
- European Society for Medical Oncology Lifetime Achievement Award (2017)
See also
- Cancer (2015 PBS film)
References
Source of article : Wikipedia
0 Comments