Differential Signaling Pathways in Medulloblastoma: Nano-biomedicine Targeting Non-coding Epigenetics to Improve Current and Future Therapeutics

Author:

Sokolov Daniil1ORCID,Sharda Neha1ORCID,Banerjee Aindrila2,Denisenko Kseniia1ORCID,Basalious Emad B.3ORCID,Shukla Hem4ORCID,Waddell Jaylyn1ORCID,Hamdy Nadia M.5ORCID,Banerjee Aditi1ORCID

Affiliation:

1. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, MD 21201, USA

2. Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA

3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Al Kasr Al Aini 11562, Cairo, Egypt

4. Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA

5. Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Abassia 11566, Cairo, Egypt

Abstract

Background: Medulloblastomas (MDB) are malignant, aggressive brain tumors that primarily affect children. The survival rate for children under 14 is approximately 72%, while for ages 15 to 39, it is around 78%. A growing body of evidence suggests that dysregulation of signaling mechanisms and noncoding RNA epigenetics play a pivotal role in this disease Methodology: This study conducted an electronic search of articles on websites like PubMed and Google. The current review also used an in silico databases search and bioinformatics analysis and an extensive comprehensive literature search for original research articles and review articles as well as retrieval of current and future medications in clinical trials. Results: This study indicates that several signaling pathways, such as sonic hedgehog, WNT/β-catenin, unfolded protein response mediated ER stress, notch, neurotrophins and TGF-β and ERK, MAPK, and ERK play a crucial role in the pathogenesis of MDB. Gene and ncRNA/protein are also involved as an axis long ncRNA to sponge micro-RNAs that affect downstream signal proteins expression and translation affection disease pathophysiology, prognosis and present potential target hit for drug repurposing. Current treatment options include surgery, radiation, and chemotherapy; unfortunately, the disease often relapses, and the survival rate is less than 5%. Therefore, there is a need to develop more effective treatments to combat recurrence and improve survival rates. Conclusion: This review describes various MDB disease hallmarks, including the signaling mechanisms involved in pathophysiology, related-causal genes, epigenetics, downstream genes/epigenes, and possibly the causal disease genes/non-protein coding (nc)RNA/protein axis. Additionally, the challenges associated with MDB treatment are discussed, along with how they are being addressed using nano-technology and nano-biomedicine, with a listing of possible treatment options and future potential treatment modalities.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,Pharmacology

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