Department of Life and Consumer Sciences, University of South Africa, Cnr Pioneer Road and Christiaan de Wet Road, Florida, Johannesburg 1710, South Africa.
Cells. 2024 Jun 29;13(13):1124. doi: 10.3390/cells13131124.
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.
Hdm2 和 Hdm4 是结构同源物，可调节肿瘤抑制蛋白 p53。由于一些肿瘤表达野生型 p53，因此 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 的活性和稳定性方面发挥关键作用。此外，Hdm2 和 Hdm4 在许多癌症中过度表达，其中一些表达野生型 Tp53。由于实验证据表明，激活野生型 Tp53 可以增强某些检查点抑制剂的抗肿瘤活性，因此靶向 Hdm2 和 Hdm4 的药物可能是与检查点抑制剂免疫疗法联合使用的有力候选药物。但是，其他证据表明，Hdm2 和 Hdm4 的过度表达可能表明对免疫检查点抑制剂的反应不佳。这些发现需要仔细检查和审查。本文将对 Hdm2/Hdm4 伙伴关系进行全面分析。此外，本文将介绍针对 Hdm2/Hdm4/Tp53 伙伴关系的分子的药物开发的最新进展。
