Selective Estrogen Receptor Modulators as a New Therapeutic Drug Group

Concept to Reality in a Decade

Gajdos, Csaba
Jordan, Craig V.

The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL

Submitted: April 20, 2001; Revised: Aug. 29, 2001; Nov. 10, 2001; Accepted: Dec. 2, 2001

Address for correspondence: V. Craig Jordan, PhD, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, IL 60611

Fax: 312–908–1372; e-mail: [email protected]

Clinical Breast Cancer 2(4):p 272-281, January 1, 2002.

Abstract

This article provides an overview of the historical development, current research, clinical benefits, and potential future applications of the selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene. The understanding of the mechanism of action of SERMs led not only to the development of tamoxifen, the first widely used antiestrogen for breast cancer treatment, but also to its application as a chemopreventive agent. The SERM principle of antiestrogenic actions in the breast but estrogenlike actions in bone is reviewed in clinical practice through analysis of the current applications and the potential for expanding the role of SERMs. The current view of the molecular mechanism of SERM action is summarized to identify potential target sites for future research. The clinical success of tamoxifen and raloxifene for the prevention and treatment of breast cancer and osteoporosis, respectively, has encouraged the development of a range of new agents that target breast cancer, osteoporosis, coronary heart disease, and endometrial safety.