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Src Continues Aging: Current and Future Clinical Directions

Authors' Affiliations: Departments of ¹ Gastrointestinal Medical Oncology, ² Cancer Biology, and ³ Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Gary E. Gallick, Department of Cancer Biology, Box #173, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009. Phone: 713-563-4919; Fax: 713-563-5489; E-mail: ggallick{at}mdanderson.org.

Abstract

Aberrant activation of members of the Src family of nonreceptor protein tyrosine kinases is common in solid tumor malignancies and may contribute to the development and/or progression of these tumors. As a result, four Src inhibitors are now in more than 50 clinical trials for at least 14 different types of solid tumors. In this review, we briefly discuss the preclinical rationale for Src inhibitors, the development strategies most likely to be successful in the clinic, and the rationale for Src inhibitors in combination with other agents as part of a more comprehensive therapeutic strategy. As the use of Src family inhibitors in clinical trials on solid tumors is in its infancy, further studies on the roles of Src family kinases in tumor progression, chemoresistance, epidermal-to-mesenchymal transition, and other properties of tumor progression will be important in designing the most effective clinical trials using these inhibitors.

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