Pezzicoli Gaetano, Filoni Elisabetta, Gernone Angela, Cosmai Laura, Rizzo Mimma, Porta Camillo
Department of Biomedical Sciences and Human Oncology, Post-Graduate School of Specialization in Medical Oncology, University of Bari 'A. Moro', Bari, Italy.
Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy.
Cancer Manag Res. 2021 Oct 4;13:7623-7636. doi: 10.2147/CMAR.S267220. eCollection 2021.
In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician's expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combinations of mTOR inhibitors and other anti-cancer drugs.
在过去十年中，雷帕霉素作用机制靶点（mTOR）抑制剂在肾透明细胞癌（RCC）治疗中的表现未达临床医生预期。多项临床试验表明，第一代mTOR抑制剂（雷帕霉素类似物）疗效欠佳且安全性难以管控，因此在临床实践中，其应用仅限于那些已历经多线治疗失败的患者。在本综述中，我们分析了削弱这类药物疗效的主要耐药机制。此外，我们还描述了一些克服耐药机制的可能策略及其临床实验情况，尤其关注新型mTOR抑制剂以及mTOR抑制剂与其他抗癌药物的联合应用。
