当前位置: X-MOL 学术Annu. Rev. Cancer Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cancer Dependencies: PRMT5 and MAT2A in MTAP/p16-Deleted Cancers
Annual Review of Cancer Biology ( IF 4.7 ) Pub Date : 2021-03-04 , DOI: 10.1146/annurev-cancerbio-030419-033444
Katya Marjon 1 , Peter Kalev 1 , Kevin Marks 1
Affiliation  

Discovery of targeted therapies that selectively exploit the genetic inactivation of specific tumor suppressors remains a major challenge. This includes the prevalent deletion of the CDKN2A/MTAP locus, which was first reported nearly 40 years ago. The more recent advent of RNA interference and functional genomic screening technologies led to the identification of hidden collateral lethalities occurring with passenger deletions of MTAP in cancer cells. In particular, small-molecule inhibition of the type II arginine methyltransferase PRMT5 and the S-adenosylmethionine-producing enzyme MAT2A each presents a precision medicine approach for the treatment of patients whose tumors have homozygous loss of MTAP. In this review, we highlight key aspects of MTAP, PRMT5, and MAT2A biology to provide a conceptual framework for developing novel therapeutic strategies in tumors with MTAP deletion and to summarize ongoing efforts to drug PRMT5 and MAT2A.

中文翻译:


癌症依赖性:MTAP / p16缺失癌症中的PRMT5和MAT2A

发现选择性利用特定肿瘤抑制因子的基因失活的靶向疗法仍然是一个重大挑战。这包括CDKN2A / MTAP基因座的普遍缺失,这是近40年前首次报道的。RNA干扰和功能基因组筛选技术的最新出现导致鉴定出伴随MTAP的乘客缺失而在癌细胞中发生的潜在附带致死性。尤其是,对II型精氨酸甲基转移酶PRMT5和产生S-腺苷甲硫氨酸的酶MAT2A的小分子抑制作用均提供了一种精确的医学方法,可用于治疗其MTAP纯合缺失的患者。在这篇综述中,我们重点介绍了MTAP,PRMT5和MAT2A生物学的关键方面,从而为开发具有MTAP缺失的肿瘤的新型治疗策略提供了概念框架,并总结了对PRMT5和MAT2A进行药物开发的努力。

更新日期:2021-03-05
down
wechat
bug