Annals of Oncology Advance Access originally published online on May 16, 2008
Annals of Oncology 2008 19(8):1379-1386; doi:10.1093/annonc/mdn291
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Targeting Src in breast cancer
Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
* Correspondence to: Dr R. S. Finn, Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, 11-934 Factor Building, Los Angeles, CA 90095, USA. Tel: +1-310-206-3180; Fax: +1-310-794-2277; E-mail: rfinn{at}mednet.ucla.edu
The clinical benefit of blocking oncogenic pathways in breast cancer and other malignancies has validated this approach and ushered in the era of molecularly targeted therapeutics. Src and its family members make up the largest group of nonreceptor tyrosine kinases. In laboratory models, these proteins have been shown to play a critical role in cellular growth and proliferation, angiogenesis, and invasion and metastasis. In addition, Src plays an important role in osteoclast activation and bone resorption, which are often aberrantly activated in the setting of bone metastases. Given its role in these functions, blocking Src kinase would be predicted to have a broad therapeutic benefit in patients with Src-dependent cancers. In this review, we highlight the rationale for targeting Src in breast cancer, including laboratory and clinical data implicating it in these signaling pathways, and review small-molecule tyrosine kinase inhibitors currently in clinical development. Identifying which patients should be selected for Src-directed therapies will be important to the clinical success of these agents. Importantly, recent preclinical data support a role for this class of inhibitors in basal-type/triple-negative breast cancer, which represents a group of patients with limited effective treatment options.
Key words: breast cancer, cancer drug development, growth factors and receptors, oncology—metastasis, Src, translational oncology—signal transduction
Received for publication February 8, 2008. Revision received April 15, 2008. Accepted for publication April 16, 2008.
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