Genomic instability as a major mechanism for acquired resistance to EGFR tyrosine kinase inhibitors in cancer

The mutation-mediated overexpression of epidermal growth factor receptor tyrosine kinase (EGFR TK) and its activation play an important role in the cellular proliferation and epithelial tumorigenesis.A series of inhibitors targeting the intracellular tyrosine kinase (TK) domain of EGFR have been developed and applied to clinical practice.Although these inhibitors safely and effectively restrain tumor cell prolifera-tion and prolong survival in some patients,acquired resis-tance ultimately arises.DNA mutations contribute to drug-induced cancer-cell resistance.