Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131, Naples, Italy.
Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", 88100, Catanzaro, Italy.
Crit Rev Oncol Hematol. 2020 Mar;147:102886. doi: 10.1016/j.critrevonc.2020.102886. Epub 2020 Jan 29.
In several tumors the PI3K/AKT/mTOR pathway is frequently disrupted, an event that results in uncontrolled cell proliferation and tumor growth. Through the years, several compounds have been developed to inhibit the pathway at different steps: the mammalian target of rapamycin (mTOR) seemed to be the most qualified target. However, this kinase has such a key role in cell survival that mechanisms of resistance are rapidly developed. Nevertheless, clinical results obtained with mTOR inhibitors in breast cancer, renal cell carcinoma, neuroendocrine tumors and mantle cell lymphoma push oncologists to actively further develop these drugs, maybe by better selecting the population to which they are offered, through the research of predictive factors of responsiveness. In this review, we aim to describe mechanisms of resistance to mTOR inhibitors, from preclinical and clinical perspectives.
在一些肿瘤中，PI3K/AKT/mTOR 通路经常被破坏，这一事件导致细胞不受控制地增殖和肿瘤生长。多年来，已经开发出几种化合物来抑制该通路的不同步骤：雷帕霉素的哺乳动物靶标（mTOR）似乎是最有资格的靶点。然而，这种激酶在细胞存活中起着如此关键的作用，以至于很快就会产生耐药机制。尽管如此，mTOR 抑制剂在乳腺癌、肾细胞癌、神经内分泌肿瘤和套细胞淋巴瘤中的临床疗效促使肿瘤学家积极进一步开发这些药物，也许可以通过研究反应性的预测因素，更好地选择提供给它们的人群。在这篇综述中，我们旨在从临床前和临床角度描述 mTOR 抑制剂的耐药机制。
