SRC kinase inhibition: Targeting bone metastases and tumor growth in prostate and breast cancer

Prostate and breast cancer cells preferentially metastasize to bone, whereupon a complex interaction between metastatic tumor cells, osteoclasts, and osteoblasts results in the development of bone lesions that cause significant pain and patient morbidity. For patients with bone lesions, the goals of treatment are to decrease tumor growth, prevent further metastases, and inhibit tumor-associated bone pathology. Preclinical data suggest that SRC, a nonreceptor tyrosine kinase, is an important signaling molecule during the processes of osteoclast-mediated bone resorption, tumor growth, and metastasis, and that SRC has a role in hormone receptor signaling and resistance. As such, SRC represents a logical target for the treatment of advanced metastatic prostate or breast cancer. SRC-targeting agents, including dasatinib, saracatinib, and bosutinib, are currently in clinical development for patients with solid tumors. Preliminary data from phase 1/2 trials, including tumor responses and bone-specific activity in patients with prostate or breast cancer, demonstrate that SRC inhibitors have potential in the clinical setting. Data arising from ongoing and future clinical trials will confirm whether SRC inhibitors provide clinical benefits for patients with advanced disease. (C) 2009 Elsevier Ltd. All rights reserved.