Src signaling pathways in prostate cancer

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.

Annatto Tocotrienol Induces a Cytotoxic Effect on Human Prostate Cancer PC3 Cells via the Simultaneous Inhibition of Src and Stat3

“…Consequently, further options are needed as alternatives to docetaxel. It has been reported that overexpression of a nonreceptor tyrosine kinase, Src, during the transition from an androgen-dependent to an androgen-independent state in prostate cancer contributes to a poorer prognosis and reduced overall survival (3). Src is an integrator of divergent signals, facilitating the action of other oncogenic signal proteins, making it an attractive target for the treatment of several human tumors (3).…”

“…It has been reported that overexpression of a nonreceptor tyrosine kinase, Src, during the transition from an androgen-dependent to an androgen-independent state in prostate cancer contributes to a poorer prognosis and reduced overall survival (3). Src is an integrator of divergent signals, facilitating the action of other oncogenic signal proteins, making it an attractive target for the treatment of several human tumors (3). In addition, in prostate cancer, androgen-independent prostate cancer cells develop the ability to survive and thrive by stimulating oncogenic pathways that Src regulates (3).…”

“…Src is an integrator of divergent signals, facilitating the action of other oncogenic signal proteins, making it an attractive target for the treatment of several human tumors (3). In addition, in prostate cancer, androgen-independent prostate cancer cells develop the ability to survive and thrive by stimulating oncogenic pathways that Src regulates (3). Src inhibitors, currently in phase III of clinical trials, are a promising treatment option for patients with androgen-independent prostate cancer (3).…”

Role and inhibition of Src signaling in the progression of liver cancer

“…The catalytic domain possesses the intrinsic tyrosine kinase activity of the molecule and is followed by a C-terminal regulatory domain [16]. The intricacy regulations of the activity of the SFKs have been summarized before [9,10,17].…”

“…Recently, the Src signaling pathways in prostate cancer had been reviewed by Varkaris et al [10] Illuminating the underlying mechanisms of SRC signaling in HCCs is required for improving diagnosis, therapy and prognosis. In this study, we reviewed newly found regulation pathway of SRC signaling, and novel molecules that directly or indirectly targeted Src signaling which can be utilized in the treatment of liver cancer.…”