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Clinical Pharmacology

The Role of Src in Solid Tumors

Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA

Key Words. c-Src • Solid tumors • Src family kinases • Molecular inhibitors

Correspondence: Deric L. Wheeler, Ph.D., Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, 600 Highland Avenue, K4/364 CSC, Madison, Wisconsin 53792-0600, USA. Telephone: 608-262-7837; Fax: 608-263-9947; e mail: dlwheeler{at}wisc.edu

Received January 19, 2009; accepted for publication June 7, 2009; first published online in THE ONCOLOGIST Express on July 6, 2009.

Disclosures: Deric L. Wheeler: Research funding/contracted research: Bristol-Myers Squibb; Mari lida: None; Emily F. Dunn: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

The proto-oncogene c-Src (Src) encodes a nonreceptor tyrosine kinase whose expression and activity are correlated with advanced malignancy and poor prognosis in a variety of human cancers. Nine additional enzymes with homology to Src have been identified and collectively are referred to as Src family kinases (SFKs). Together, SFKs represent the largest family of nonreceptor tyrosine kinases and interact directly with receptor tyrosine kinases, G-protein-coupled receptors, steroid receptors, signal transducers and activators of transcription, and molecules involved in cell adhesion and migration. These interactions lead to a diverse array of biological functions including proliferation, cell growth, differentiation, cell shape, motility, migration, angiogenesis, and survival. Studies investigating mutational activation of Src in human cancers suggest that this may be a rare event and that wild-type Src is weakly oncogenic. Thus, the role of Src in the development and progression of human cancer remains unclear. Recently, it was suggested that increased SFK protein levels and, more importantly, SFK tyrosine kinase activity are linked to cancer progression and metastatic disease by facilitating the action of other signaling proteins. This accumulating body of evidence indicates that SFKs may represent a promising therapeutic target for the treatment of solid tumors. This review discusses the role of SFKs in solid tumors and the recent therapeutic advances aimed at targeting this family of tyrosine kinases in cancer.

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