Impact of mSWI/SNF epigenetic complexes on ionizing radiotherapy resistance in malignant diseases: A comprehensive view in oncology

Abstract

The mSWI/SNF chromatin remodeling complexes are critical regulators of genomic stability, particularly in their role in orchestrating DNA repair and modulating cellular responses to ionizing radiation therapy. Their involvement has positioned these molecular complexes as key factors in determining radiosensitivity in human malignant diseases. The present review delves into the biomedical contributions of specific mSWI/SNF subunits, including ARID1A, SMARCB1, SMARCA4, PBRM1, and BRD9, highlighting their pivotal roles in influencing tumor responses to radiotherapy. Evidence suggests that the loss of function in these subunits, often due to mutations, disrupts DNA repair pathways, thereby compromising genomic integrity and enhancing susceptibility to radiation-induced damage. Emerging preclinical studies have underscored the potential of exploiting these vulnerabilities through pharmacological targeting of mSWI/SNF complexes. Inhibition of these complexes can impair DNA damage repair mechanisms, creating a synthetic lethality effect by using a combined epigenetic therapy with ionizing radiation protocols. This dual approach not only amplifies the therapeutic efficacy of radiotherapy but also broadens the spectrum of potential strategies for oncological therapy. However, further investigation into the molecular mechanisms underlying these epigenetic interactions is essential for optimizing oncological therapies and paving the way for clinical applications aimed at enhancing radiotherapy outcomes in cancer patients.