The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles

Lung cancer is the leading cause of cancer-related mortality worldwide. Although the PI3K/Akt/mTOR signaling pathway has recently been considered as one of the most altered molecular pathways in this malignancy, few articles reviewed the task. In this review, we aim to summarize the original data obtained from international research laboratories on the oncogenic alterations in each component of the PI3K/Akt/mTOR pathway in lung cancer. This review also responds to questions on how aberrant activation in this axis contributes to uncontrolled growth, drug resistance, sustained angiogenesis, as well as tissue invasion and metastatic spread. Besides, we provide a special focus on pharmacologic inhibitors of the PI3K/Akt/mTOR axis, either as monotherapy or in a combined-modal strategy, in the context of lung cancer. Despite promising outcomes achieved by using these agents, however, the presence of drug resistance as well as treatment-related adverse events is the other side of the coin. The last section allocates a general overview of the challenges associated with the inhibitors of the PI3K pathway in lung cancer patients. Finally, we comment on the future research aspects, especially in which nano-based drug delivery strategies might increase the efficacy of the therapy in this malignancy.