Many patients may fail to respond initially to a tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR). Other patients may respond to TKI therapy for a period of time, only to develop a resistant tumor over time.
Some of the factors associated with resistance to EGFR TKI may include:
(1) wild type EGFR
(2) EGFR mutation not responsive to the TKI (T790M, others)
(3) KRAS mutation
(4) amplification of c-MET
(5) mutation in BRAF
(6) mutation in PIK3CA
(7) overexpression of insulin-like growth factor 1 receptor (IGF1R)
(8) overexpression of HGF (hepatocyte growth factor)
(9) loss of PTEN expression (phosphatase and tensin homolog) with overexpression of p-AKT (phosphorylated AKT)
(10) ALK gene fusion
(11) change in the host’s TKI pharmacokinetics (decreased absorption, increased metabolism or excretion)
If the tumor can find a way to bypass the blocked pathway, then it will. A long-term response to targeted therapy may require multiple agents that address different pathways.
To read more or access our algorithms and calculators, please log in or register.
