CDK4/6抑制剂联合mTOR抑制剂在乳腺癌中的作用机制

CDK-RB-E2F通路和PI3K-AKT-mTOR通路对乳腺癌耐药机制起到了关键作用。通过对两个通路的研究发现,在治疗激素受体阳性的乳腺癌时,CDK4/6抑制剂与内分泌药物联合使用可以提高患者的生存率,mTOR抑制剂也显示出抗肿瘤的实力。最近的研究表明,mTOR抑制剂和CDK4/6抑制剂联合使用可以进一步抑制CDK-RB-E2F通路激活,协同控制肿瘤细胞增殖。同时发现CDK4/6抑制剂耐药患者的CDK-RB-E2F通路重新激活,仍对mTOR抑制剂敏感。还有研究表明CDK4/6抑制剂和mTOR抑制剂可以通过自噬作用协同控制肿瘤的发生。本文针对两药联合在乳腺癌中的作用机制进行综述。

Action for CDK4/6 inhibitors combined with mTOR inhibitors in breast cancer and its mechanism

Many studies indicate that the CDK-RB-E2F pathway and the PI3K-AKT-mTOR pathway play key roles in the mechanism of drug resistance in breast cancer.Through studies of two pathways,the combination of CDK4/6 inhibitors and endocrine drugs can improve the survival rate of patients with hormone receptor-positive breast cancer,and mTOR inhibitors also show the anti-tumor strength.Recent studies have shown that the combination of mTOR inhibitors and CDK4/6 inhibitors can further inhibit the activation of the CDK-RB-E2F pathway and synergistically controls tumor cell proliferation.It was also found that the CDK-RB-E2F pathway in CDK4/6 inhibitor-resistant patients was reactivated and sensitive to mTOR inhibitor.Other studies have also shown that CDK4/6 inhibitors and mTOR inhibitors can synergistically control tumorigenesis through autophagy.This article reviews several mechanisms of combination of two drugs.