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阐明PI3K/Akt/mTOR信号通路的表观遗传调控机制在人类恶性肿瘤中的作用

Elucidation of the Role of the Epigenetic Regulatory Mechanisms of PI3K/Akt/mTOR Signaling Pathway in Human Malignancies.

作者信息

Mohite Rupali, Doshi Gaurav

机构信息

Department of Pharmacology, Toxicology and Therapeutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, V.M. Road, Vile Parle (W), Mumbai, India.

出版信息

Curr Cancer Drug Targets. 2024;24(3):231-244. doi: 10.2174/1568009623666230801094826.

Abstract

The PI3K/Akt/mTOR pathway modulates cell growth, proliferation, metabolism, and movement. Moreover, significant studies have shown that the genes involved in this pathway are frequently activated in human cancer. Observational and computational modeling of the PI3K/AKt/ mTOR pathway inhibitors has been explored in clinical trials. It has been observed that the effectiveness and safety evidence from clinical studies and various inhibitors of this route have been given FDA approval. In this review article, we focused on the processes behind the overactivation of PI3K/Akt/mTOR signaling in cancer and provided an overview of PI3K/Akt/mTOR inhibitors as either individual drugs or a combination of different doses of drugs for different types of cancer. Furthermore, the review discusses the biological function and activation of the PI3K/AKt/mTOR signaling and their role in the development of cancers. Additionally, we discussed the potential challenges and corresponding prediction biomarkers of response and resistance for PI3K/Akt/m- TOR inhibitor development. The article focuses on the most current breakthroughs in using the PI3K/Akt/mTOR pathway to target certain molecules.

摘要

PI3K/Akt/mTOR信号通路调节细胞生长、增殖、代谢和运动。此外,大量研究表明,该信号通路中的相关基因在人类癌症中经常被激活。PI3K/AKt/mTOR信号通路抑制剂的观察性研究和计算模型已在临床试验中进行探索。据观察,来自临床研究的有效性和安全性证据以及该信号通路的各种抑制剂已获得美国食品药品监督管理局(FDA)的批准。在这篇综述文章中,我们重点关注癌症中PI3K/Akt/mTOR信号过度激活背后的过程,并概述了PI3K/Akt/mTOR抑制剂作为单一药物或不同剂量药物组合用于不同类型癌症的情况。此外,该综述讨论了PI3K/AKt/mTOR信号的生物学功能和激活及其在癌症发展中的作用。此外,我们还讨论了PI3K/Akt/mTOR抑制剂开发中潜在的挑战以及相应的反应和耐药性预测生物标志物。本文重点介绍了利用PI3K/Akt/mTOR信号通路靶向某些分子的最新突破。

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