Institute of Oncology Research, Faculty of Biomedical Sciences, USI, 6500 Bellinzona, Switzerland.
Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100 Catanzaro, Italy.
Int J Mol Sci. 2020 Feb 5;21(3):1060. doi: 10.3390/ijms21031060.
The activation of the PI3K/AKT/mTOR pathway is a main driver of cell growth, proliferation, survival, and chemoresistance of cancer cells, and, for this reason, represents an attractive target for developing targeted anti-cancer drugs. There are plenty of preclinical data sustaining the anti-tumor activity of dual PI3K/mTOR inhibitors as single agents and in combination in lymphomas. Clinical responses, including complete remissions (especially in follicular lymphoma patients), are also observed in the very few clinical studies performed in patients that are affected by relapsed/refractory lymphomas or chronic lymphocytic leukemia. In this review, we summarize the literature on dual PI3K/mTOR inhibitors focusing on the lymphoma setting, presenting both the three compounds still in clinical development and those with a clinical program stopped or put on hold.
PI3K/AKT/mTOR 通路的激活是癌细胞生长、增殖、存活和化疗耐药的主要驱动因素,因此,它是开发靶向抗癌药物的有吸引力的靶点。有大量的临床前数据支持双 PI3K/mTOR 抑制剂作为单一药物以及联合用于淋巴瘤的抗肿瘤活性。在针对复发/难治性淋巴瘤或慢性淋巴细胞白血病患者进行的极少数临床研究中,也观察到了临床反应,包括完全缓解(特别是滤泡性淋巴瘤患者)。在这篇综述中,我们总结了关于双 PI3K/mTOR 抑制剂的文献,重点介绍了仍处于临床开发阶段的三种化合物以及已停止或暂停临床计划的化合物。