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Src signaling pathways in prostate cancer

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Abstract

Knowledge of the molecular events that contribute to prostate cancer progression has created opportunities to develop novel therapy strategies. It is now well established that c-Src, a non-receptor tyrosine kinase, regulates a complex signaling network that drives the development of castrate-resistance and bone metastases, events that signal the lethal phenotype of advanced disease. Preclinical studies have established a role for c-Src and Src Family Kinases (SFKs) in proliferation, angiogenesis, invasion and bone metabolism, thus implicating Src signaling in both epithelial and stromal mechanisms of disease progression. A number of small molecule inhibitors of SFK now exist, many of which have demonstrated efficacy in preclinical models and several that have been tested in patients with metastatic castrate-resistant prostate cancer. These agents have demonstrated provocative clinic activity, particularly in modulating the bone microenvironment in a therapeutically favorable manner. Here, we review the discovery and basic biology of c-Src and further discuss the role of SFK inhibitors in the treatment of advanced prostate cancer.

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Authors and Affiliations

  1. Department of Genitourinary Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Unit 1374 1155 Pressler St, Houston, TX, 77030, USA

    Andreas Varkaris, John C. Araujo, Gary E. Gallick & Paul G. Corn

  2. David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

    Andreas Varkaris & Gary E. Gallick

  3. Evangelismos General Hospital, University of Athens, Athens, Greece

    Andreas Varkaris & Anastasia D. Katsiampoura

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  1. Andreas Varkaris
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  2. Anastasia D. Katsiampoura
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  3. John C. Araujo
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  4. Gary E. Gallick
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  5. Paul G. Corn
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Correspondence to Paul G. Corn.

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Varkaris, A., Katsiampoura, A.D., Araujo, J.C. et al. Src signaling pathways in prostate cancer. Cancer Metastasis Rev 33, 595–606 (2014). https://doi.org/10.1007/s10555-013-9481-1

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