Is Src a Viable Target for Treating Solid Tumours?

B.      Elsberger; B.      Stewart; O.      Tatarov; J.      Edwards

Abstract

Src was the first proto-oncogene to be discovered. Since then the role of Src has been extensively studied in vitro. Src is a key regulator of multiple signal transduction pathways and plays a significant part in cellular transformation. Dysfunction of Src, through overexpression or increased activation, has profound effects on basic cellular functions. Elevated Src expression and/or activation is evident across a wide range of solid tumour types, highlighting its place in carcinogenesis and making it an attractive therapeutic target.

In this review, we discuss in vitro and in vivo data examining the role of Src in the different cellular processes involved in oncogenesis and metastasis, covering the association of Src with increased cell proliferation and survival, decreased cellular adhesion, increased cell motility and invasiveness, accelerated/advanced angiogenesis and pathogenic bone activity. We also review evidence gathered from human tumour tissue and translational research studies that further substantiates the role of Src in oncogenesis. A summary of Src inhibitors currently being developed and trialled as therapeutic agents is provided to underline Src as a potential molecular target for solid tumour therapy. Further clinical data are needed to conclusively demonstrate that Src inhibitors have clinical utility in the treatment of solid tumors.

Keywords: Proto-oncogene, Src, targeted therapy, tyrosine kinase.

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