Gerald D. Aurbach Award for Outstanding Translational Research
V. Craig Jordan, OBE, DSc, PhD
The Gerald D. Aurbach Award for Outstanding Translational Research is presented to V. Craig Jordan, OBE, DSC, PhD, for the discovery and development of a novel group of medicines called Selective Estrogen Receptor Modulators (SERMs) applied to address the treatment and prevention of major diseases in women. Ideally, the SERMs switch off estrogen target tissues in the breast and uterus to prevent cancer and switch on estrogen target tissues to maintain bone density or lower circulating low-density lipoprotein cholesterol to prevent coronary heart disease.
The clinical success for the translational concept of selective ER modulation has stimulated future applications for selective nuclear receptor modulators in medicine.
The discovery that tamoxifen is metabolically activated to 4-hydroxytamoxifen (4-OHT) with a 100-fold increased affinity for the ER not only provided a new research tool to study anti-estrogen action in vitro but also opened the door for the synthesis of the new SERMs raloxifene, bazedoxifene, and lasofoxifene. Tamoxifen and raloxifene are the pioneering SERMs whose diverse applications in breast cancer treatment and prevention, as well as osteoporosis, have contributed to improving or extending countless women’s lives. Five SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, ospemiphene) are FDA approved to treat diseases and conditions in women including: the treatment of all stages of breast cancer; indolent lesions of epithelial origin (formerly DCIS); and risk reduction in high-risk women, osteoporosis, dyspareunia, or help reduce the symptoms of menopause.
Few other mechanism-based group of medicines have such broad applications or such an impact in society. Raloxifene, ospemiphene, and bazedoxifene all have scientific origins through structural and pharmacologic original discoveries in Jordan’s laboratory. Lasofoxifene, which is not FDA approved, demonstrates many qualities of an ideal SERM: high potency for the prevention of osteoporosis (the daily dose is 1/100th the daily dose of raloxifene); a reduction of ER-positive breast cancer; and reduction in strokes and coronary heart disease. But unlike tamoxifen, there is no increase in endometrial cancer. The clinical success for the translational concept of selective ER modulation has stimulated future applications for selective nuclear receptor modulators in medicine.
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