期刊
ANNUAL REVIEW OF CANCER BIOLOGY, VOL 5, 2021
卷 5, 期 -, 页码 371-390出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-cancerbio-030419-033444
关键词
MTAP; p16; PRMT5; MAT2A; synthetic lethal
类别
Discovery of targeted therapies exploiting genetic inactivation of specific tumor suppressors, such as MTAP deletion, remains a challenge. However, inhibiting PRMT5 and MAT2A presents a precision medicine approach for these tumors with MTAP loss.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据