EGFR and neoplasm: Other possible routes for acquired resistance to TKIs include: metalloproteinase 17 (ADAM17) mediated autocrine activation of ERBB2 and ERBB3, amplification of EGFR, hyperactivation of downstream signaling components that circumvent EGFR inhibition, cellular changes that alter the bioavailability of the inhibiting drugs, and drug-resistance through ATP-binding cassette GE (ABCG2) transporter which actively pumps the cytotoxic agent out of the tumor cells [48,81].