MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario
The University of Texas MD Anderson Cancer Center · Sarah Cannon · +3 more institutions
Abstract
Homozygous deletions in the gene encoding methylthioadenosine phosphorylase (MTAP) occur in ∼10% of patients with cancer, including up to 45% in some tumor types, and may be associated with poor prognosis. MTAP deficiency causes accumulation of its catabolic target methylthioadenosine (MTA) that outcompetes S-adenosyl methionine (SAM) for binding to protein arginine methyltransferase 5 (PRMT5), partially inhibiting PRMT5 activity as a posttranslational regulator of a variety of critical cellular functions. Prior anticancer treatments developed to target PRMT5 exhibited high rates of dose-limiting hematologic toxicities because of a lack of selectivity for tumor cells. More recently, several agents have been…
Citation impact
- FWCI
- 47.03
- Percentile
- 100%
- References
- 0
Authors
5Topics & keywords
- Protein arginine methyltransferase 5
- Synthetic lethality
- Cancer
- Methionine
- Methyltransferase
- Regulator
- Gene
- No poverty