Predictor of Trastuzumab (Herceptin) Resistance in Breast Cancer Cells Identified
July 25, 2013
Researchers in the Okayama University Graduate School of Natural Science and Technology have revealed one of resistance mechanisms in breast cancer cells against the antibody drug, trastuzumab (Herceptin).
The findings were published online on June 21, 2013 in the journal Journal of Cancer.
Trastuzumab is a monoclonal antibody targeted against the HER2 (ErbB2) tyrosine kinase receptor. The efficacy of trastuzumab depends on its ability to induce an immune response. When binding to HER2 (ErbB2), trastuzumab promotes apoptosis in breast cancer cells via antibody-dependent cellular cytotoxicity (ADCC). However, the majority of breast cancer patients with HER2 (ErbB2)-overexpressing tumors develop trastuzumab resistance. Therefore, identifying the molecular mechanisms that contribute to trastuzumab resistance is very important.
Professor Seno and his group have shown that caveolin-1 expression in breast cancer cells facilitates ErbB2 endocytosis. When ErbB2 is absorbed into the cell, the attached trastuzumab is also absorbed. As a result, ADCC functions are attenuated. Therefore, caveolin-1 expression in breast cancer cells could be a predictive factor to estimate how cancer cells are likely to respond to trastuzumab treatment.
In addition, a novel molecular targeted cancer drug of that efficacy is independent of cavelion-1 expression level has developed successfully as a result of this study.
The study was supported by the Japan Society for the Promotion of Science (JSPS) [Kakenhi #24510151, #23650598].
Mototaka Senda, Ph.D.
Intellectual Property Office, Organization for Research Promotion and Collaboration, Okayama University
Fremont, California USA
Masaharu Seno, Ph.D.
Graduate School of Natural Science and Technology, Okayama University, Okayama Japan