Factors and molecular mechanisms of radiation resistance in cancer cells

Abstract

Purpose

The aim of this work is to review the published studies on radiation resistance mechanisms and molecular markers involved in different tumors. The revision has been focused in the last 5 years (2016–2021).

Conclusions

Radioresistance is a cause of concern as it causes failure of radiation therapy and subsequent tumor relapse. Combination chemotherapy and radiation therapy are clinically successful in treating many types of tumors. Despite continued improvements in cancer treatment, locoregional recurrence or metastatic spread continues to occur in a high proportion of patients after being treated with radiation therapy or combination treatments. There is strong evidence that cancer stem cells contribute to radiation resistance, contributing to treatment failure. The mechanisms of radiation resistance in different tumors are not fully understood. A better understanding of cancer stem cells and the associated signaling pathways that regulate radiation resistance will open up new strategies for treating cancer by radiation therapy. Radiation can damage malignant cells mainly by the induction of DNA double-strand breaks. However, in some tumors appear resistant cells that repopulate the tumor following therapy leading over time to the failure of the treatment. Native mechanisms and induced pathways are the cause of radiation resistance. It has been described that numerous molecular markers acting through numerous mechanisms of action involved in radiation resistance, such as apoptosis resistance, alterations of cell growth, proliferation and DNA repair, hypoxia, increase in invasiveness and migration capacity, cell cycle alterations, and expression of heat shock proteins, among others. Therefore, resistance to radiation is a multifactorial phenomenon that, in different cell types, occurs through different regulatory mechanisms in which different molecules intervene. Resistance can be acquired by altering different regulatory pathways in different tumors. The knowledge of radiation resistance markers could help in the classification and treatment of patients with more aggressive tumors.

Keywords:

• Radiation
• resistance
• cancer treatment
• biomarker
• DNA damage

Author contributions

Conception and design: JCAP, MJRG; Collection and/or assembly of data: JCAP, AMBM, AGV, FSP, MJRG; Data analysis and interpretation: JCAP, AMBM, AGV, FSP, MJRG; Design and generation of tables and figures: MJRG; Writing the first draft of the manuscript: JCAP; Writing the final version of the manuscript: MJRG; Study supervision: MJRG; Approved the final version of the paper for publication: JCAP, AMBM, AGV, FSP, MJRG.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Notes on contributors

Juan C. Alamilla-Presuel

Juan C. Alamilla-Presuel, MD, is a PhD student at the Department of Radiology and Physical Medicine, Faculty of Medicine, University of Málaga, Málaga, Spain.

Antonio M. Burgos-Molina

Antonio M. Burgos-Molina, MSc, Med, PhD, is an Instructor of Immunology and Immunopathology at the Department of Surgical Specialties, Biochemistry and Immunology, Faculty of Medicine, University of Málaga, Málaga, Spain.

Alejandro González-Vidal

Alejandro González-Vidal, BSc, MSc, MEd, is a member of the Radiobiology research group, at the Department of Radiology and Physical Medicine, Faculty of Medicine, University of Málaga, Málaga, Spain; and a teacher at MEDAC, Zaragoza, Spain.

Francisco Sendra-Portero

Francisco Sendra-Portero, MD, PhD, is an Associate Professor of Radiology and Physical Medicine and Department Chair, at the Department of Radiology and Physical Medicine, Faculty of Medicine, University of Málaga, Málaga, Spain.

Miguel J. Ruiz-Gómez

Miguel J. Ruiz-Gómez, MSc, PhD, is an Associate Professor of Radiology and Physical Medicine and Head of the Radiobiology research group, at the Department of Radiology and Physical Medicine, Faculty of Medicine, University of Málaga, Málaga, Spain.