A group of scientists report that the gene FKBPL can predict whether women with breast cancer will respond to tamoxifen. They say that when it is found in high levels in breast cancer, it indicates a good response to tamoxifen and a better chance of survival. Conversely low levels of FKBPL indicate a poor response.
The study was led by Tracy Robson, Ph.D., and Hayley McKeen, Ph.D., from the School of Pharmacy Queen’s University Belfast. Their findings are published in Cancer Research in a paper titled “FKBPL Regulates Estrogen Receptor Signaling and Determines Response to Endocrine Therapy.”
FKBPL is an estrogen-responsive gene that interacts with estrogen receptor α (ERα) and regulates its levels. In this study, the researchers explored the effects of FKBPL on breast cancer proliferation.
Breast cancer cells stably overexpressing FKBPL became dependent on estrogen for their growth and were dramatically more sensitive to the anti-estrogens tamoxifen and fulvestrant. FKBPL knockdown, however, reversed this phenotype. FKBPL knockdown also decreased the levels of the cell cycle inhibitor p21WAF1 and increased ERα phosphorylation on Ser118 in response to 17β-estradiol and tamoxifen.
In support of the likelihood that these effects explained FKBPL-mediated cell growth inhibition and sensitivity to endocrine therapies, FKBPL expression was correlated with increased overall survival and distant metastasis-free survival in breast cancer patients.
The next step is to assess levels of this gene in breast cancer samples from large numbers of patients who were treated with tamoxifen. “In the next three years we should have a clearer indication of whether our research can benefit the patient,” notes Dr. Robson.