PDF(Pubmed)
Abstract：
Hdm2 and Hdm4 are structural homologs that regulate the tumor suppressor protein, p53. Since some tumors express wild-type p53, Hdm2 and Hdm4 are plausible targets for anticancer drugs, especially in tumors that express wild-type p53. Hdm4 can enhance and antagonize the activity of Tp53, thereby playing a critical role in the regulation of p53\'s activity and stability. Moreover, Hdm2 and Hdm4 are overexpressed in many cancers, some expressing wild-type Tp53. Due to experimental evidence suggesting that the activation of wild-type Tp53 can augment the antitumor activity by some checkpoint inhibitors, drugs targeting Hdm2 and Hdm4 may be strong candidates for combining with checkpoint inhibitor immunotherapy. However, other evidence suggests that the overexpression of Hdm2 and Hdm4 may indicate poor response to immune checkpoint inhibitors. These findings require careful examination and scrutiny. In this article, a comprehensive analysis of the Hdm2/Hdm4 partnership will be conducted. Furthermore, this article will address the current progress of drug development regarding molecules that target the Hdm2/Hdm4/Tp53 partnership.
摘要：
Hdm2和Hdm4是调控肿瘤抑制蛋白的结构同源物,.由于一些肿瘤表达野生型p53，Hdm2和Hdm4是抗癌药物的合理靶点，尤其是在表达野生型p53的肿瘤中。Hdm4可以增强和拮抗Tp53的活性,从而在调节p53的活性和稳定性中起关键作用。此外，Hdm2和Hdm4在许多癌症中过度表达，一些表达野生型Tp53。由于实验证据表明野生型Tp53的激活可以通过一些检查点抑制剂增强抗肿瘤活性，针对Hdm2和Hdm4的药物可能是联合检查点抑制剂免疫疗法的有力候选药物.然而,其他证据表明，Hdm2和Hdm4的过表达可能表明对免疫检查点抑制剂的反应较差。这些发现需要仔细检查和审查。在这篇文章中,将对Hdm2/Hdm4伙伴关系进行全面分析。此外，本文将介绍目前针对Hdm2/Hdm4/Tp53合作伙伴关系的分子的药物开发进展。
