Targeting SRC and epidermal growth factor receptor in colorectal cancer: rationale and progress into the clinic.
Src is a non-receptor protein tyrosine kinase that affects proliferation, angiogenesis, differentiation, migration, invasion, and regulation of apoptosis in colorectal cancer cells. Src activation is a frequent early epigenetic event in colorectal cancer, and is progressively increased in metastatic tumors as compared with primary tumors. Src has also been implicated as a component of epidermal growth factor receptor (EGFR) signal transduction. In particular, Src, as a mediator of receptor transactivation, can uniquely activate EGFR in the absence of EGFR ligand, and a Src inhibitor is synergistic with an EGFR monoclonal antibody in vitro in eliciting growth inhibition. Src inhibition is also synergistic in vivo with platinum chemotherapeutics, further increasing the potential of combination regimens with Src inhibitors. The current Src inhibitors in clinical trials are reviewed.
Kopetz
Scott
S
Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX.