Several mutations have been recently described in the tyrosine kinase domain of EGFR.
Mutations in the tyrosine kinase domain of the epidermal growth factor receptor have prognostic significance, since patients with EGFR-mutant NSCLC have prolonged disease-free survival, compared with those with wild-type disease, regardless of the treatment received.
58,59) These are in-frame insertions in exon 20 that target the corresponding tyrosine kinase domain region, as in EGFR-insertion mutations.
The tyrosine kinase domain is encoded by exons 18 to 24, while the C-terminal domain is encoded by exons 25 to 28.
The most clinically advanced EGFR inhibition strategies include small-molecule inhibition of the intracellular tyrosine kinase domain and monoclonal antibody-mediated blockade of the extracellular ligand-binding domain.
Upon ligand binding, ErbB receptors form homo- or heterodimers leading to activation of the tyrosine kinase domain and the triggering of a complex downstream signalling cascade.
Inhibition of EGFR may be achieved by a variety of mechanisms including utilising antisense or small interference RNA to suppress EGFR gene expression , the use of tyrosine kinase inhibitors that target the intracellular tyrosine kinase domain, or the use of monoclonal antibodies that target the extracellular domain and inhibit ligand binding.
In this case, both BCR-ABL and ABL tyrosine kinase domains