Bioactive PI3-kinase/Akt/mTOR Inhibitors in Targeted Lung Cancer Therapy

Abstract

One of the central signaling pathways with a regulatory effect on cell proliferation and survival is Akt/mTOR. In many human cancer types, for instance, lung cancer, the overexpression of Akt/mTOR has been reported. For this reason, either targeting cancer cells by synthetic or natural products affecting the Akt/mTOR pathway down-regulation is a useful strategy in cancer therapy. Direct inhibition of the signaling pathway or modulation of each related molecule could have significant feedback on the growth and proliferation of cancer cells. A variety of secondary metabolites has been identified to directly inhibit the AKT/mTOR signaling, which is important in the field of drug discovery. Naturally occurring nitrogenous and phenolic compounds can emerge as two pivotal classes of natural products possessing anticancer abilities. Herein, we have summarized the alkaloids and flavonoids for lung cancer treatment together with all the possible mechanisms of action relying on the Akt/mTOR pathway down-regulation. This review suggested that in search of new drugs, phytochemicals could be considered as promising scaffolds to be developed into efficient drugs for the treatment of cancer. In this review, the terms "Akt/mTOR", "Alkaloid", "flavonoid", and "lung cancer" were searched without any limitation in search criteria in Scopus, PubMed, Web of Science, and Google scholar engines.

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…This has suggested the usage of combinatorial therapeutic regimens directed against OSCC. Consistently, treatment of OSCC patients with PI3K/AKT inhibitors combined with cytostatic/cytotoxic chemotherapeutics has provided promising results [189,190].…”

“…Since several human malignancies display PI3K/AKT dysregulation, antagonists of this pathway have been developed that exert anticancer activity [190]. As for OSCC, PI3K/AKT inhibitors hamper the proliferation and invasion of the carcinoma cells and increase their sensitivity to conventional antitumor therapies [191][192][193][194].…”

SNAI1 as a Biomarker for Prognostic Prediction and Targeted Therapy in Lung Squamous Cell Carcinoma

“…Therefore, targeting the mTOR pathway for down-regulation has emerged as a promising strategy in lung cancer therapy (11)(12)(13)(14)(15).…”

Exploiting new strategies in combating head and neck carcinoma: A comprehensive review on phytochemical approaches passing through PI3K/Akt/mTOR signaling pathway

“…Noteworthy, in true alkaloids, the nitrogen atom is part of the nitrogen‐containing heterocyclic ring, whereas, in protoalkaloids, this is not the case (Dey et al, 2020). Among various health‐promoting properties of alkaloids, anticancer effects through modulation of the PI3K/Akt/mTOR signaling pathway have recently gained a great deal of attention (Ghareghomi et al, 2023).…”