PI3K/Akt/mTOR信号通路抑制剂在转移性结直肠癌中的研究进展

Research Progress in PI3K/Akt/mTOR Signaling Pathway Inhibitors in Metastatic Colorectal Cancer

转移性结直肠癌(mCRC)一直是临床治疗的难点,而分子靶向药物的出现,有效改善了mCRC患者的生存期,但是已在临床推广应用的分子靶向药物耐药性的产生却阻碍了基因靶向治疗的进一步发展。磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路抑制剂作为近年来新出现的靶向药物,为各种常见肿瘤提供了新的治疗方案。目前PI3K/Akt/mTOR通路抑制剂的抗肿瘤特性已得到临床认可,但由于信号通路相互交联的特点,特别是针对信号通路中的突变或过表达的情况,联合多细胞毒性药物或多通路抑制方案有可能解决mCRC耐药的局面。

The treatment of metastatic colorectal cancer(mCRC) has always been a difficult point in the clinical practice,and the emergence of molecular targeted drugs has effectively improved the survival period of mCRC patients,but the generation of drug resistance has hindered the further development of gene targeted therapy.The phosphatidylinositol- 3-kinase /protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway inhibitor,as a newly emerged targeted drug in recent years,provides a new treatment scheme for various common tumors.Currently,the effective anti-tumor nature of PI3K/Akt/mTOR pathway inhibitors has been clinically recognized.However,due to the cross-linking characteristics of the signaling pathways,especially in the case of mutations or overexpression in the signaling pathways,the combination of multi-cytotoxic drugs or multi-pathway inhibition schemes may effectively solve the situation of drug resis- tance in mCRC treatment.