Moving beyond tamoxifen: Drug discovery and the future of selective hormone receptor modulators

Fox Chase Cancer Center's V. Craig Jordan highlights emerging strategies for cancer prevention at the 2008 AAAS Annual Meeting

How did a failed contraceptive become the first targeted therapy for the treatment of breast cancer" The transformation of tamoxifen, from cast-off to lifesaver, laid the foundation for a new class of therapeutics – selective estrogen receptor modulators – that could treat or prevent a variety of human diseases, including cancer and osteoporosis, according to V. Craig Jordan, OBE, Ph.D., D.Sc., a researcher at the Fox Chase Cancer Center in Philadelphia.

Today at the 2008 Annual Meeting of the American Association for the Advancement of Science, Jordan reports on efforts to use the lessons learned about tamoxifen to develop new hormone receptor-related drugs for both women and men. His presentation will be part of a symposium, held from 1:45 p.m. to 4:45 p.m., entitled “Progress in Cancer Prevention.”

“As both a preventative and therapeutic agent, tamoxifen has been credited with saving the lives of more than a half million women over the last 30 years,” says Jordan, the Alfred G. Knudson Jr., M.D., Ph.D., Chair in Cancer Research at Fox Chase. “The process of discovery that made tamoxifen a reality has given us insights into molecular mechanisms that are currently being used to advance the creation and refinement of better drugs.”

In the 1970s, Jordan’s laboratory pioneered the work that turned tamoxifen into a cancer therapy, which then jump-started a field of study into so-called designer estrogens. These drugs, called selective estrogen receptor modulators (SERMS), can have different effects on their targets, estrogen receptors, depending on where the receptor is located within a woman's body. The SERM raloxifene, for example, exhibits an anti-estrogen activity that can prevent cancer in breast tissue, but in other tissue the same drug has an estrogen-like effect that increases bone density. Currently, raloxifene, which was also developed in Jordan’s laboratory, is approved in post-menopausal women to prevent osteoporosis and treat breast cancer.