REPROGRAMMING CANCER CELL PHYSIOLOGY THROUGH EPIGENETIC MECHANISMS: INSIGHTS INTO NEURO-ONCOLOGY

Abstract

The interactive nature of epigenetic control and cancer cell physiology has come to be one of the primary paradigms in tumorigenesis studies, especially in the difficult field of neuro-oncology. Epigenetic modifications, (a DNA methylation, histone acetylation, chromatin remodelling and non-coding RNA-mediated regulation) are reversible and very sensitive to intrinsic and extrinsic signals, unlike genetic mutations which are permanent changes in the DNA sequence. This plasticity permits cancer cells to restructure their transcriptional networks, to respond to the microenvironmental stresses, and to develop the features of malignancy, including persistent proliferation, immune evasion, and resistance to therapy. Epigenetic deregulation will acquire a particular importance in the context of primary and metastatic brain tumors because biochemical restraint of the central nervous system and blood-brain barrier is unique to this organ. The following review compiles the existing information on the epigenetic processes involved in cancer cell reprogramming, with a particular emphasis on glioblastoma multiforme and other malignant central nervous system neoplasms. We also discuss the new epigenetic therapies, such as histone deacetylase inhibitors, DNA methyltransferase inhibitors, and epigenetic-editing platforms, considering their potential to rescue the pathological phenotypes and restore the normal functioning of the cells. Lastly, we touch on the translation issues and the future perspective of incorporating epigenetic approaches to precision neuro-oncology.

Keywords: epigenetics, cancer reprogramming, neuro-oncology, glioblastoma, DNA methylation, histone modification, chromatin remodeling, epigenetic therapy.