Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106


Is Src a Viable Target for Treating Solid Tumours?

Author(s): B. Elsberger, B. Stewart, O. Tatarov, J. Edwards.


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, SH domains, Phosphorylation, platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), vascular endothe-lial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), CDK = cyclin-dependent kinase, ECM = extracellular matrix, ERK = extracellular signal-regulated kinase, FAK = focal adhesion kinase, GF = growth factor, MEK = mitogen-activated protein kinase kinase, PI3K = phosphatidylinositol-3-kinase, extracellular matrix (ECM), urokinase plasminogen activator receptor (u-PAR), osteo-clasts, (IGF I and II), FGFs, PDGFs, (ER/PgR), SH2/SH3 inhibitors, UCS15A, AP22408, KX2 391, dasatinib, saracatinib, bosutinib, Lymphocytosis

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Article Details

Year: 2010
Page: [683 - 694]
Pages: 12
DOI: 10.2174/156800910793605802
Price: $58