自噬与肿瘤EGFR抑制剂耐药的研究进展

Advances of Autophagy and EGFR Inhibitors Resistance in Cancer

表皮生长因子受体(epidermal growth factor receptor,EGFR)这种酪氨酸激酶受体在许多类型实体肿瘤的发生及生长过程中起着主要作用,因而针对性地应用EGFR抑制剂已被批准作为多种类型肿瘤的治疗方法.然而,先天性或获得性耐药问题限制了这类药物的疗效.自噬作为细胞内废弃物降解的一种方式,被认为与肿瘤EGFR抑制剂耐药相关. EGFR抑制剂能诱导自噬,然而该作用是双向的.自噬既能减弱EGFR抑制剂的细胞毒性作用而介导肿瘤耐药,也会在过度自噬的情况下促进细胞死亡而逆转肿瘤耐药.因此,调节自噬水平有可能为克服肿瘤患者EGFR抑制剂耐药提供更多思路.

Epidermal growth factor receptor(EGFR), a kind of tyrosine kinase receptors, plays an important role in many types of solid tumors. Using EGFR inhibitors has been approved as a treatment for multiple types of tumors. However, innate or acquired resistance has limited the efficacy of these drugs. Autophagy, a means of degradation of intracellular wastes, is considered to be related with EGFR inhibitors resistance in cancer. EGFR inhibitors can induce autophagy, but this function is biphasic. Autophagy can not only attenuate the cytotoxic effects of EGFR inhibitors to mediate drug resistance, but also can promote cell death to reverse resistance in the case of excessive autophagy. Thus, autophagy regulation is likely to provide more ideas for conquering EGFR inhibitors resistance in patients with tumors.