Novel molecular targets in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is the third leading cause of cancer-related death worldwide. A high mortality rate and resistance to treatment protocols due to a heterogeneous molecular pathogenesis has made discovering the key etiologic molecular alterations of the utmost importance. The remarkable role played by epigenetic modifications in repressing or activating many cancer-related genes and forming new epigenetic signatures can affect cancer initiation and progression. Hence, targeting the key epigenetic drivers could potentially attenuate cancer progression. MLLs, ARID1A and EZH2 are among the major epigenetic players that are frequently mutated in GACs. In this paper, we have proposed the existence of a network between these proteins that, together with PCAF and KDM6A, control the 3D chromatin structure and regulate the expression of tumor suppressor genes (TSGs) and oncogenes in GAC. Therefore, we suggest that manipulating the expression of EZH2, PCAF, and KDM6A or their downstream targets may reduce the cancerous phenotype in GAC. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Roya Ramezankhani, Roya Solhi, Hamidreza Aboulkheyr Es, Massoud Vosough, Moustapha Hassan. Novel molecular targets in gastric adenocarcinoma. Pharmacology & therapeutics. 2021 Apr;220:107714

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PMID: 33172596

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