Understanding the molecular basis of radioresistance in lung cancer: A comprehensive review

Abstract

Lung cancer (LC) remains the most common malignancy in both genders and is the leading cause of cancer-related death worldwide. Despite significant advances in therapeutic approaches, radiotherapy (RT) continues to be one of the main approaches to LC treatment. However, radioresistance represents a major challenge to effective disease management and contributes significantly to treatment failure and poor prognosis. Radioresistance can be intrinsic, existing before treatment, or acquired during RT. It is a highly complex and multifactorial mechanism involving various cellular and molecular processes that are not yet fully understood. Key mechanisms contributing to radioresistance include enhanced DNA damage repair, cell cycle redistribution, inhibition of apoptosis, disruption of intracellular signaling pathways, interaction with the tumor microenvironment, autophagy-mediated survival, cancer stem cell-related resistance, and deregulation of non-coding ribonucleic acids. Understanding these pathways is essential for identifying new therapeutic targets and developing strategies to overcome resistance and improve patient outcomes. This review provides a comprehensive overview of the molecular mechanisms underlying radioresistance in LC.

Keywords

Lung cancer / Radiotherapy / Radioresistance

Acknowledgements

The authors would like to thank The Centre National pour la Recherche Scientifique et Technique (CNRST) of Morocco for funding Attouahri Fatima Zohra’s “PhD-ASsociate Scholarship - PASS’.”

Funding

This paper has been prepared within the framework of the project funded by Mohammed VI Polytechnic University & OCP Foundation (TNI 2024 program).

Conflict of interest

The authors declare they have no competing interests.

Author contributions

Conceptualization: Mouna Ababou, Khaoula Errafii, Mohammed El Mzibri

Visualization: Boutaina Addoum, Leila Benbacer, Samira Mimount, Bouchra El Mchichi, Abdelhamid Barakat, Hanane El Ouazzani, Ismail Rhorfi, Ahmed Abid

Writing – original draft: Fatima Zohra Attouahri

Writing – review & editing: Khalid Ennibi, Khaoula Errafii, Mohammed El Mzibri

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Not applicable.

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