Titles and Affiliations
Research Professor, Department of Medicine and Life Sciences
Universitat Pompeu Fabra
Research Director, Consortium Mar Health Park of Barcelona and Hospital del Mar Institute of Medical Research
Director, Preclinical Research Program
Research area
Developing novel therapies that utilize the power of the immune system to treat breast cancer.
Impact
The HER2 protein is a growth promoting protein and when overexpressed on the surface of breast cancer cells can fuel the growth and development of HER2-positive breast cancer. While HER2-targeted therapies, particularly antibody-drug conjugates (ADCs), have been very effective, these breast cancers can become resistant to them. Dr. Arribas and his colleagues are focusing on the mechanisms of resistance by examining HER2 biology and the role of the immune system. They have shown that HER2, particularly a truncated form called p95HER2, not only fuels breast cancer growth but also dampens the immune system’s ability to attack the tumor. This immunosuppressive action appears to limit the efficacy of ADCs like trastuzumab durextecan (Enhertu®/T-DXd). In the past few years, T-DXd has transformed outcomes for patients with HER2-positive breast cancer. As clinicians are increasingly using T-DXd in earlier stages of the disease, the number of patients facing treatment resistance may rise sharply. Dr. Arribas and his team are addressing the urgent need to understand how resistant tumors evolve biologically and immunologically after T-DXd exposure—their results will inform the next therapy steps for these patients.
What’s next
T-DXd works like a guided missile: an antibody recognizes HER2 on tumor cells and delivers a chemotherapy payload directly to them. When tumors stop responding, doctors have no clear rules for choosing the next therapy. Using CAR-T cell (Chimeric Antigen Receptor T-cells) technology, Dr. Arribas has developed a novel construct where immune cells called T-cells have been engineered to target p95HER2 while sparing healthy tissues. In collaboration with clinical colleagues, Dr. Arribas is now testing it in the first-ever CAR-T therapy clinical trial in breast cancer, the phase 1 CATHERINE trial. This trial is enrolling patients with HER2-positive advanced breast cancer and testing the feasibility of exploiting tumor-specific HER2 alterations therapeutically. In the laboratory, his team developed patient-derived models that recapitulate resistant tumors. Through these two lines of study, his team hopes to identify the molecular and immune mechanisms that allow tumors to escape T-DXd. His work aims to turn an open biological question into concrete, biology-informed options for women whose tumors have progressed on the best available treatment.
Biography
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.
