Targeting pi3k/akt/mtor signaling in cell lung cancer: basic to clinical studies

Zeinab Zohrabzadeh,1,* Mohammad amin dehghani,2 Reza kiani rad ,3 Fatemeh dehghani ,4

1. School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2. Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3. School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4. Department of Genetics, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract


Introduction

In human malignancy such as non-small cell lung cancer (nsclc), the pi3k-akt-mtor pathway is normally deregulated. generally, the tumor proliferation, development and growth of nsclc is regulated by the pi3k/akt/mtor pathway, which is targeted by several new inhibitors. in clinical trials or preclinical studies, different types of new inhibitors that target this pathway have been detected.

Methods

In this research, the english article published in the pubmed database were searched using the keywords of mtor inhibitors, targeted therapy, non-small cell lung cancer, pi3k inhibitors, and pi3kakt-mtor pathway.

Results

Various clinical and preclinical studies have assessed different inhibitors of the pi3k pathway. in this regard, the detected inhibitors are dual pi3k-mtor, dual mtorc1-mtorc2, rapamycin and rapalogs for mtor inhibition, pan and selective inhibitors of pi3k, and akt inhibitors. auranofin is a medication approved by food and drug association (dfa) and has confirmed pharmacokinetic and safety profiles in humans. this drug has strong inhibitory effects in multiple sites of the pi3k/atk/mtor axis in human lung cancer cells, which makes it possible to quickly translate its novel use for lung cancer treatment.

Conclusion

According to the results of the study, a potential therapeutic agent in nsclc could be the inhibitors of pi3k signaling. therefore, in anti-lung cancer therapy that is mediated by auranofin, we can inhibit the whole pathway of pi3k/akt/mtor as a new mechanism of action.

Keywords

non-small cell lung cancer‏; pi3kakt-mtor pathway; mtor inhibitor; pi3k inhibitor; targeted therapy