MTAP loss: a possible therapeutic approach for glioblastoma

Abstract

Glioblastoma is the most lethal form of brain tumor with a recurrence rate of almost 90% and a survival time of only 15 months post-diagnosis. It is a highly heterogeneous, aggressive, and extensively studied tumor. Multiple studies have proposed therapeutic approaches to mitigate or improve the survival for patients with glioblastoma. In this article, we review the loss of the 5′-methylthioadenosine phosphorylase (MTAP) gene as a potential therapeutic approach for treating glioblastoma. MTAP encodes a metabolic enzyme required for the metabolism of polyamines and purines leading to DNA synthesis. Multiple studies have explored the loss of this gene and have shown its relevance as a therapeutic approach to glioblastoma tumor mitigation; however, other studies show that the loss of MTAP does not have a major impact on the course of the disease. This article reviews the contrasting findings of MTAP loss with regard to mitigating the effects of glioblastoma, and also focuses on multiple aspects of MTAP loss in glioblastoma by providing insights into the known findings and some of the unexplored areas of this field where new approaches can be imagined for novel glioblastoma therapeutics.

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

“…Glioma is a highly aggressive and highly lethal malignant tumor of the central nervous system ( Liu et al, 2021 ). In particular, glioblastoma, a grade IV glioma, is the most aggressive primary brain tumor, with a recurrence rate of up to 90% and a survival rate of only 15 months after diagnosis ( Patro et al, 2022 ). Abnormal protein palmitoylation of glioma brain tissue compared to normal brain tissue in the central nervous system correlates with the abnormal expression of some zDHHCs in gliomas ( Tang et al, 2022a ).…”

Exploring Therapeutic Avenues in Lung Cancer: The Epigenetic Perspective

“…This makes PRMTs appealing targets for therapeutic intervention [88]. A common PRMT dysregulation, specifically of PRMT5, has been correlated with the loss of MTAP (5-methylthioadenosine phosphorylase) expression in lung cancer, resulting in the accumulation of methylthioadenosine (MTA), which significantly inhibits PRMT5 activity [89,90]. The loss of MTAP expression, as a result of deletion, stands out as a significant area of interest due to its prevalence in over 10% of diverse human malignancies, including in NSCLC [91].…”