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Journal of Clinical Oncology, Vol 20, Issue 1 (January), 2002: 325-334
© 2002 American Society for Clinical Oncology

BIOLOGY OF NEOPLASIA

STI571: A Paradigm of New Agents for Cancer Therapeutics

By Michael J. Mauro, Michael O’Dwyer, Michael C. Heinrich, Brian J. Druker

From the Leukemia Program, Division of Hematology and Medical Oncology, Oregon Health Sciences University and Veterans Affairs Medical Center, Portland, OR.

Address reprint requests to Brian J. Druker, MD, Oregon Health Sciences University, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97201; email: drukerb{at}ohsu.edu

ABSTRACT: STI571 exemplifies the successful development of a rationally designed, molecularly targeted therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to specifically inactivate this abnormality. Issues related to clinical trials of molecularly targeted agents are discussed, including dose selection, optimizing therapy, and predicting response, as are possible mechanisms of resistance to STI571. Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies are explored.


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