Role of chromatin remodeling and immunopharmacology in cancer therapy.

Abstract

Epigenetic modifications play a crucial role in cancer, influencing cellular physiology, extracellular matrix (ECM) remodeling, and immune responses. With growing emphasis on chromatin remodeling and the epigenetic regulation of immunity, these regulatory pathways and related players have become focal points of oncological investigations. Epigenetic manipulation of immune system components has emerged as a promising strategy in cancer treatment. Several FDA-approved "epi-drugs" target the epigenome to modulate immune responses and offer new opportunities across different cancers. DNA repair pathways contribute significantly to the avoidance of cancer initiation and also contribute to cellular resistance in cancer treatment. Chromatin remodelers such as INO80, Fun30, and RAD54 play essential roles in DNA damage response (DDR) through homologous recombination and non-homologous end-joining pathways, and their dysregulation leads to genome instability and tumor progression. Chromatin remodeling complexes, including SWI/SNF and CHD families, are frequently altered across various cancer types, further highlighting their role in cancer pathophysiology. Targeting these chromatin modifiers and associated DNA repair mechanisms may provide novel therapeutic options. In addition, combining epigenetic modulators with immunotherapies has shown promise in enhancing responses to immune checkpoint blockade. Epigenetic drugs such as histone deacetylase (HDAC) inhibitors and DNA methylation inhibitors are being explored for their synergistic effects with immunotherapy. While the interplay between chromatin remodeling, DNA repair, and immune responses provides a strong framework for developing targeted oncological strategies, further research is required to better understand these interactions and optimize their clinical application.