Epigenetic-Based Therapy—A Prospective Chance for Medulloblastoma Patients’ Recovery

Abstract

Medulloblastoma (MB) is one of the most frequent and malignant brain tumors in children. The prognosis depends on the advancement of the disease and the patient’s age. Current therapies, which include surgery, chemotherapy, and irradiation, despite being quite effective, cause significant side effects that influence the central nervous system’s function and cause neurocognitive deficits. Therefore, they substantially lower the quality of life, which is especially severe in a developing organism. Thus, there is a need for new therapies that are less toxic and even more effective. Recently, knowledge about the epigenetic mechanisms that are responsible for medulloblastoma development has increased. Epigenetics is a phenomenon that influences gene expression but can be easily modified by external factors. The best known epigenetic mechanisms are histone modifications, DNA methylation, or noncoding RNAs actions. Epigenetic mechanisms comprehensively explain the complex phenomena of carcinogenesis. At the same time, they seem to be a potential key to treating medulloblastoma with fewer complications than past therapies. This review presents the currently known epigenetic mechanisms that are involved in medulloblastoma pathogenesis and the potential therapies that use epigenetic traits to cure medulloblastoma while maintaining a good quality of life and ensuring a higher median overall survival rate.

Whole genome sequencing of nearly isogenic WMI and WLI inbred rats identifies genes potentially involved in depression and stress reactivity

“…Among these genes, GNAT 2 has a variant in human (rs6537837) that was reported to be associated with unipolar depression with a genome wide significance of p = 1e−6 46 , while Prlr and Nlrp1a were implicated in depression-like behavior in animal models 47 , 48 . Further, Pou6f2 , Kdm5a , Reep3 , Wdfy3 have been implicated in psychiatric diseases such as autism 49 – 51 and Pigr was found to be involved in response to psychological stress 52 , 53 .…”

Celastrol can inhibit the growth of SHH medulloblastoma: In vitro and in vivo studies

“…WNT-MB is found in the embryonic lower rhombic lip (LRL), whereas Sonic Hedgehog (SHH)-driven medulloblastoma (SHH-MB) and non-WNT/non-SHH MB are found in the cerebellar precursor matrix [3]. The MB is primarily treated with surgical resection, radiotherapy, and chemotherapy as adjuvant therapy [4]. However, treatment outcomes are often suboptimal, leading to severe long-term side effects [3].…”

Special Issue “Tumors of the Nervous System: New Insights into Signaling, Genetics and Therapeutic Targeting”

“…Current therapies, despite being quite effective, unfortunately cause adverse effects that influence the central nervous system’s function, thus lowering the quality of life of patients. Epigenetic-based potential therapies for MB that could ensure a higher survival rate while maintaining a good quality of life are described in this review [ 3 ].…”