Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Laboratory Sciences, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.
J Cancer Res Clin Oncol. 2023 Nov;149(16):15293-15310. doi: 10.1007/s00432-023-05277-x. Epub 2023 Aug 18.
The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway regulates proliferation, survival and metabolism, and its dysregulation is one of the most frequent oncogenic events across human malignancies. Over the last two decades, there has been significant focus on the clinical development of PI3K pathway inhibitors. More than 40 different inhibitors of this axis have reached various stages of clinical trials, but only a few of them have been approved by the Food and Drug Administration (FDA) for cancer treatment. These clinical results, however, could be improved given the importance of PI3K signaling in cancer and its role in linking cancer growth with metabolism. In this systematic review, after a glance at PI3K/AKT/mTOR pathway and its different inhibitors, we retrieved registered clinical trials evaluating the efficacy and safety of PI3K/AKT/mTOR inhibitors on Clinicaltrials.gov. Following the extraction of the data, finally we analyzed 2250 included studies in multiple steps, beginning with an overview and moving on to the details about type of malignancies, inhibitors, and treatment strategies. We also took a closer look at more than 100 phase III-IV clinical trials to pinpoint promising therapies, hoping that presenting a comprehensive picture of current clinical trials casts a flash of light on what remains to be done in future clinical trials of PI3K/AKT/mTOR inhibitors in human malignancies.
磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路调节增殖、存活和代谢，其失调是人类恶性肿瘤中最常见的致癌事件之一。在过去的二十年中，人们对 PI3K 途径抑制剂的临床开发给予了高度关注。已经有超过 40 种该轴的不同抑制剂进入了各种临床试验阶段，但只有少数几种被美国食品和药物管理局（FDA）批准用于癌症治疗。然而，鉴于 PI3K 信号在癌症中的重要性及其在将癌症生长与代谢联系起来的作用，这些临床结果可以得到改善。在本系统综述中，我们首先简要介绍了 PI3K/AKT/mTOR 通路及其不同的抑制剂，然后在 Clinicaltrials.gov 上检索了评估 PI3K/AKT/mTOR 抑制剂在癌症治疗中的疗效和安全性的已注册临床试验。在提取数据后，我们最终在多个步骤中分析了 2250 项纳入的研究，从概述开始，然后详细了解恶性肿瘤的类型、抑制剂和治疗策略。我们还仔细研究了 100 多项 III 期-IV 期临床试验，以确定有前途的治疗方法，希望呈现当前临床试验的全貌，为未来人类恶性肿瘤中 PI3K/AKT/mTOR 抑制剂的临床试验指明方向。
