Protein tyrosine kinase signaling diversity and susceptibility to targeted kinase inhibitors

Protein kinases, including tyrosine kinases, are one of the largest classes of proteins implicated in cancer development and progression. Recent discovery of selective therapies targeting tyrosine kinase receptor signaling has provided encouraging clinical results. Clinical trials with anti-EGFR, anti-ErbB2/Her2, anti-Bcr-Abl and others have demonstrated the clinical utility of tyrosine kinases as therapeutic targets and as surrogate markers to guide the selection of patients susceptible to respond to treatment. This success has been tempered in part because resistance to targeted therapies is now documented to occur in experimental models and in patients, which hampers therapeutic efficacy. Mechanisms of resistance include cell heterogeneity in target expression, mutations in target's encoding genes, and compensatory signaling mechanisms. This paper provides a brief overview on the diversity of tyrosine kinase signaling and the impact on cancer cell response to targeted tyrosine kinase inhibitors.