With the advent of tyrosine kinase inhibitors
with efficacy against only specific mutations, detecting these mutations has become increasingly important in the clinical laboratory setting.
Small molecules functioning as tyrosine kinase inhibitors
are used to block EGFR signaling.
This form of EGFR-activating mutation is generally associated with resistance to EGFR tyrosine kinase inhibitors
although insertions at or before position 768 can be associated with sensitivity.
Small-molecule tyrosine kinase inhibitors
expose cells to anti-cancer drugs because they block ABC transporter efflux.
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.
More recently, a Phase II study presented at the 2007 annual meeting of the American Society of Clinical Oncology examined the use of a VEGF receptor tyrosine kinase inhibitor
, axitinib, in addition to docetaxel (80 mg/[m.
JAVELIN Renal 100 is a Phase Ib, open-label, multicentre, multiple-dose study investigating avelumab in combination with INLYTA (axitinib), a tyrosine kinase inhibitor
from Pfizer, for the treatment of treatment-naAaAaAeA patients with advanced RCC.
IRESSA is an EGFR tyrosine kinase inhibitor
that acts by blocking the transmission of signals involved in the growth and spread of tumours.
Imatinib mesylate: Gleevec[R], Novartis; a tyrosine kinase inhibitor
approved in 2001 to treat CML; now standard of care