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

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.

Automated summary

The Akt/mTOR signaling pathway plays a regulatory role in cell proliferation and survival. Overexpression of Akt/mTOR has been observed in many human cancer types, including lung cancer. Targeting the Akt/mTOR pathway through the use of synthetic or natural products is a promising strategy for cancer therapy. Inhibition of the pathway or modulation of related molecules can have a significant impact on cancer cell growth and proliferation.