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Joaquin Arribas, PhD
Director, Medical Oncology Research Program
Vall d'Hebron Institute of Oncology
Goal: To identify new targets that will improve response to HER2-targeted therapies.
Impact: Dr. Arribas is testing novel therapies developed by his team to treat a subtype of HER2-positive tumors that tend to be particularly aggressive and resistant to treatment. His work may lead to a new combination treatment to improve the effectiveness of HER2-targeted therapies.
What’s next: He and his team will identify methods of resistance to this drug in order to find novel therapeutic approaches to overcome them.
While HER2-directed therapies such as trastuzumab have been effective in treating many HER2-positive breast cancers, not all tumors respond to these drugs. Others become resistant during the course of therapy. Dr. Arribas has developed novel therapies that induce an immune reaction against tumor cells that may benefit patients who have a particularly aggressive and treatment resistant type of HER2-positive breast cancer.
Full Research Summary
Research area: Developing combination therapies to improve clinical outcomes in patients with HER2-positive breast cancer.
Impact: HER2-positive breast cancer accounts for approximately 20 to 30 percent of all breast cancer cases. HER2-targeting treatments are effective in treating many of these tumors, but some tumors do not respond to them, while others become resistant during therapy. Dr. Arribas has developed novel therapies that target a type of HER2-positive tumor that is characterized by the presence of a truncated from of HER2 called p95HER2. This form of HER2 is particularly active and promotes malignant transformation of the cancer cell. His work could pave the way for new combination treatments for p95HER2-positive tumors.
Current research: Dr. Arribas and his colleagues are conducting laboratory studies to identify and fully test novel approaches to improve outcomes in patients with an aggressive type of HER2-positive breast cancer.
What he’s learned so far: Dr. Arribas and his colleagues have shown that a subgroup of HER2-postiive tumors express a truncated form of HER2, p95HER2, in addition to a full-length HER2 protein. This truncated form of HER2 is completely absent in normal tissues. Moreover, the tumors that express p95HER2 are particularly aggressive. They have recently developed novel therapies to target p95HER2- by inducing an immune reaction against these tumor cells. Recent studies have shown that tumor relapses and side effects of anti-tumor therapies are due, at least in part, to the accumulation of damaged cells that undergo a resting state known as cellular senescence. Therefore, Dr. Arribas and his team have also developed a model that will allow them to study tumor cell senescence to identify ways to effectively eliminate these dormant cancer cells.
What’s next: Dr. Arribas and his colleagues will continue to develop novel therapies to direct immune cells against the p95HER2 subtype of tumors in an effective and safe manner. To anticipate the clinical needs associated with the use of these novel therapies, they will also characterize the mechanisms of resistance to identify specific vulnerabilities of these resistant cells that may be targeted by new combination strategies. Ultimately, they hope to be able to eliminate senescent cells to improve patient response to treatment.
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.