Director, Medical Oncology Research Program
Vall d'Hebron University Hospital
Seeking to identify new targets to improve response to HER2-targeted therapies
A novel HER2-targeted therapy is being tested and biomarkers of response will help to select patients most likely to benefit from the therapy.
Dr. Arribas' work may lead to a new combination treatment to improve the effectiveness of HER2 targeted therapies.
HER2 positive (HER2+) breast cancer accounts for approximately 20-30 percent of all breast cancer cases. Despite the clinical success of HER2-targeting drugs such as trastuzumab, some tumors do not respond to these treatments. Others become resistant during the course of therapy, and the drug stops working. Combination therapies may be a way to address drug resistance and improve clinical outcome.
Work by Dr. Arribas' laboratory has shown that HER2 causes breast cancer cells to stop growing, called “senescence”. Paradoxically, even in this "quiet" state, tumor cells can produce a wealth of factors that can promote tumor growth and metastasis and thereby contribute to tumor progression.
Using different breast cancer models, Dr. Arribas and his team have shown that HER2-induced senescent cells help non-senescent cancer cells to metastasize. A subgroup of HER2-positive tumors express, in addition to the full-length HER2 protein, some HER2 fragments, collectively known as p95HER2, which are particularly active and promote malignant transformation very efficiently. In fact, p95HER2-positive tumors tend to be particularly aggressive and resistant to treatment.
Dr. Arribas and his team recently developed a novel drug to target p95HER2-positive tumors. This drug induces an immune reaction against tumor cells. In the upcoming year, they will continue to characterize this novel therapy and determine the percentage of patients that may benefit from this novel therapy. Use of this drug may dampen an undesired effect of senescent cells and complement current anti-tumor therapies.
Dr. Joaquin Arribas is the Director of Preclinical Research Program at Vall d’Hebron Institute of Oncology in Barcelona, Spain, where he leads a group focused on the study of growth factors, growth factor receptors, and the proteases involved in remodeling the cell surface. He is a member of the Editorial Board of the Journal of Biological Chemistry, Translational Oncology, and CDB Protein Systems.
Dr. Arribas is member of the Spanish and American Societies of Biochemistry and Molecular Biology and President of the Committee for the Evaluation of Cancer Research project at the Institute of Health Carlos III, a major public funding agency in Spain.
Dr. Arribas completed his undergraduate studies in biochemistry at the University of Madrid, where he subsequently worked on the regulation of the catalytic activities of the proteasome and received a PhD in biology in 1991. Sponsored by a fellowship from the Spanish Ministry of Education and Science, he joined Memorial Sloan Kettering Cancer Center in New York as a postdoctoral fellow to work with Dr. Joan Massague (1992-1996) on the proteolytic processing of transmembrane growth factors. In 1997, he joined the Oncology Department at Hospital Vall d'Hebron as a staff scientist and was promoted to lead the oncology research department in 2001. Dr. Arribas’s research has been recognized by the European Molecular Biology Organization (EMBO), which honored him with a Young Investigator Program (YIP) Award. Also, Dr. Arribas received the Beckman Coulter Award conferred on the Best Young Spanish Investigator in Biochemistry and Molecular Biology.