4.8 Review

Histone acetyltransferases CBP/p300 in tumorigenesis and CBP/p300 inhibitors as promising novel anticancer agents

期刊

THERANOSTICS
卷 12, 期 11, 页码 4935-4948

出版社

IVYSPRING INT PUBL
DOI: 10.7150/thno.73223

关键词

CBP/p300; gene transcription; tumorigenesis; small molecule inhibitors; cancer therapy

资金

  1. National Health & Medical Research Council Australia
  2. National Natural Science Foundation of China
  3. Chongqing Science and Health Joint Medical Research Project [2020MSXM007]

向作者/读者索取更多资源

CBP/p300, critical drivers of oncogenesis, promote tumorigenesis and have been shown to be over-expressed in cancer cells; their inhibitors and degraders are considered promising anticancer agents that reduce H3K27ac, regulate oncogene transcription, induce cancer cell death and activate immune response.
The histone acetyltransferases CBP and p300, often referred to as CBP/p300 due to their sequence homology and functional overlap and co-operation, are emerging as critical drivers of oncogenesis in the past several years. CBP/p300 induces histone H3 lysine 27 acetylation (H3K27ac) at target gene promoters, enhancers and super-enhancers, thereby activating gene transcription. While earlier studies indicate that CBP/p300 deletion/loss can promote tumorigenesis, CBP/p300 have more recently been shown to be over-expressed in cancer cells and drug-resistant cancer cells, activate oncogene transcription and induce cancer cell proliferation, survival, tumorigenesis, metastasis, immune evasion and drug-resistance. Small molecule CBP/p300 histone acetyltransferase inhibitors, bromodomain inhibitors, CBP/p300 and BET bromodomain dual inhibitors and p300 protein degraders have recently been discovered. The CBP/p300 inhibitors and degraders reduce H3K27ac, down-regulate oncogene transcription, induce cancer cell growth inhibition and cell death, activate immune response, overcome drug resistance and suppress tumor progression in vivo. In addition, CBP/p300 inhibitors enhance the anticancer efficacy of chemotherapy, radiotherapy and epigenetic anticancer agents, including BET bromodomain inhibitors; and the combination therapies exert substantial anticancer effects in mouse models of human cancers including drug-resistant cancers. Currently, two CBP/p300 inhibitors are under clinical evaluation in patients with advanced and drug-resistant solid tumors or hematological malignancies. In summary, CBP/p300 have recently been identified as critical tumorigenic drivers, and CBP/p300 inhibitors and protein degraders are emerging as promising novel anticancer agents for clinical translation.

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。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据