Targeting Src in breast cancer

Abstract

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.