Joaquín Arribas, PhD
Director, Medical Oncology Research Program
Vall d'Hebron University Hospital Research Institute
2013-2014 BCRF Project:
HER2 is a cell surface receptor expressed at excessive levels in approximately 20% of breast cancers. This group of HER2-positive (HER2+) tumors constitutes a type of breast cancer with specific biological characteristics and therapeutic options, which include anti-HER2 antibodies and synthetic HER2 inhibitors. A subset of HER2+ tumors express, in addition to the full-length HER2 protein, some HER2 fragments, collectively known as p95HER2, which are particularly active and promote the malignant transformation very efficiently. In fact, p95HER2-positive tumors tend to be particularly aggressive and resistant to the treatment with anti-HER2 antibodies.
Through previous research funded by BCRF, Dr. Arribas has shown that the expression of p95HER2 in some breast cancer cell lines leads to premature cellular senescence, which is a natural process by which cells “age” and begin to die. These senescent cells did not proliferate but remained alive during long periods of time and produced pro-metastatic factors that helped neighboring cancer cells to be more metastatic. Therefore, inhibition of these pro-metastatic factors may constitute a novel therapeutic approach which may be particularly relevant since many of the chemo- and radiotherapies currently used result in the appearance of senescent cells.
Through previous research funded by BCRF, the Arribas team has shown in vitro that the expression of p95HER2 in some breast cancer cell lines leads to premature cellular senescence, which is a natural process by which cells “age”. These senescent cells did not proliferate but remained alive during long periods of time and produced pro-metastatic factors that helped neighboring cancer cells to be more metastatic. This year, also with funds from the BCRF the researchers have been able to show that senescent cells are constantly produced by growing tumors and feed proliferating cells with a wealth of factors that foster the malignant progression. They will soon test if the inhibition of some of the factors produced by senescent cells impairs tumor growth.
Dr. Joaquin Arribas is the Director of the Medical Oncology Research Program at Vall d'Hebron University Hospital Research Institute in Barcelona, Spain, where he leads a group focused on the study of growth factors, growth factor receptors, as well as 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 in 1987 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 in Barcelona 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 Programme (YIP) Award. Also, Dr. Arribas received the Beckman Coulter Award conferred on the Best Young Spanish Investigator in Biochemistry and Molecular Biology.