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Is Src the key to understanding metastasis and developing new treatments for colon cancer?

Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages 306–307 (2008)Cite this article

Colon cancer is the fourth most common cancer worldwide and causes half a million deaths each year.1 Colon cancer is treated by surgical resection of the tumor, but in a large proportion of patients the cancer is metastatic and cannot be cured by surgery; in most of these cases the disease carries a survival time from diagnosis of <2 years. Treatments for metastatic colon cancer are, therefore, urgently sought.

The proto-oncogene tyrosine-protein kinase Src regulates the activation of cellular proteins such as phosphoinositide 3-kinase (PI3K), protein kinase C, phospholipase and Ras. Src is already a therapeutic target for inhibitors of its activity: Dasatinib (Bristol-Myers Squibb, New York, NY), AZD0530 (AstraZeneca, Alderley Park, UK), Bosutinib (Wyeth Cambridge, MA), and KXO1(Kinex, Buffalo, NY) have all been investigated in clinical trials;2 PP1 and PP2 (Calbiochem, San Diego, CA) have been investigated only in experimental studies.3,4 Src inhibitors are being investigated because Src is activated in patients with colon cancer and colon cancer metastasis is associated with progressively elevated Src activity.2 Overexpression of a mutated active Src gene, and overexpression of a v-Src gene in mice, have both been shown to promote colon cancer metastasis.5 Conversely, silencing Src expression using small interfering RNA (siRNA) has been shown to reduce cancer cell growth in the colon cancer cell line SW48.6 Src activation in colon cancer has been linked to upregulation of Src-activating molecules (e.g. epidermal growth factor) and downregulation of Src-inactivating molecules (e.g. C-terminal src kinase and Csk-homologue kinase).6 Src can also be activated by mutations in the Src nucleotide sequence. For example, a mutation that results in constitutively activated Src has been found in 12% of patients with colon cancer.5

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  1. Cancer Biology Program, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Qld 4102, Australia j.chen4@uq.edu.au

Authors and Affiliations

  1. J Chen is a Research Officer at the Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Brisbane, Qld, Australia.,

    Jiezhong Chen

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Chen, J. Is Src the key to understanding metastasis and developing new treatments for colon cancer?. Nat Rev Gastroenterol Hepatol 5, 306–307 (2008). https://doi.org/10.1038/ncpgasthep1141

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