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Synlett 2025; 36(16): 2437-2452
DOI: 10.1055/a-2507-3598
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Small Molecules in Medicinal Chemistry

Advancements in mTOR Inhibitors for Non-Small-Cell Lung Cancer: Mechanisms, Efficacy, and Future Perspectives

Aanal Thaker‡
a   Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
,
Shrusti Patel‡
a   Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
,
Rajdeep Dey
b   Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
,
Suman Shaw
b   Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
,
Hardik Bhatt
b   Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
,
Bhumika Patel
b   Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
,
Udit Chaube  ∗
b   Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India
› Author Affiliations
This work was supported by the Minor Research Project (UID: IPNU/2024-26/144) funded by Nirma University, Ahmedabad, India.
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Abstract

This account comprehensively reviews the recent advancements in the development of mechanistic target of rapamycin (mTOR) inhibitors targeting non-small-cell lung cancer (NSCLC), focusing on their mechanisms, efficacy, and clinical trial statuses. Key small molecules such as RM-018 and RMC-4998 highlight novel approaches in targeting the KRASG12C mutation, offering enhanced potency compared to earlier inhibitors. Traditional and plant-derived compounds, including Fuzi alkaloids, salvianolic acid, and ononin, demonstrate promising antitumor activities through diverse pathways, such as the PI3K/AKT/mTOR signaling axis. Combination therapies targeting dual pathways show synergistic effects, improving treatment efficacy. The role of personalized medicine, driven by genetic profiling and pathway-specific inhibitors, is emphasized as a transformative approach in NSCLC management. These findings highlight the potential of mTOR-targeting agents as a cornerstone in advancing NSCLC therapies.

1 Introduction

2 Small-Molecule mTOR Inhibitors

3 mTOR Inhibitors in Clinical Trials

4 Conclusion and Future Directions

Key words

mTOR - small molecules - rapalogs - clinical trials - cancer


Publication History

Received: 30 November 2024

Accepted after revision: 20 December 2024

Accepted Manuscript online:
20 December 2024

Article published online:
12 February 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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