吉非替尼在非小细胞肺癌治疗中的继发耐药

吉非替尼是一种表皮生长因子受体(EGFR)酪氨酸激酶抑制剂,对非小细胞肺癌(NSCLC)有良好的抗肿瘤活性,但大多数患者最终因继发耐药出现病情进展.在发生EGFR基因突变的肺腺癌患者中,约半数吉非替尼继发耐药与二次突变有关,这种二次突变导致EGFR 790位上的苏氨酸被甲硫氨酸所取代(T790M).其他导致耐药的机制包括EGFR受体的内化现象以及MET基因扩增.

Secondary resistance of gefitinib in non-small-cell lung cancer treatment

Gefitinib (iressa),an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor,has antitumor activity in non-small-cell lung cancer (NSCLC).Despite the dramatic response to this inhibitor,most patients nevertheless ultimately have relapses because of the secondary resistance.In human lung adenocar-cinomas with EGFR mutation,a second-site point mutation that substitutes methionine for threonine at position 790(T790M) is associated with approximately half of cases of secondary resistance to gefitinib.Other mecha-nisras that contribute to gefitinib resistance include EGFR receptor internalization and MET gene amplification.