Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy.

IF 9 2区 医学 Q1 CELL BIOLOGY Journal of Biomedical Science Pub Date : 2024-01-29 DOI:10.1186/s12929-024-01004-x
Dantong Sun, Haili Qian, Junling Li, Puyuan Xing
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Abstract

MDM2 has been established as a biomarker indicating poor prognosis for individuals undergoing immune checkpoint inhibitor (ICI) treatment for different malignancies by various pancancer studies. Specifically, patients who have MDM2 amplification are vulnerable to the development of hyperprogressive disease (HPD) following anticancer immunotherapy, resulting in marked deleterious effects on survival rates. The mechanism of MDM2 involves its role as an oncogene during the development of malignancy, and MDM2 can promote both metastasis and tumor cell proliferation, which indirectly leads to disease progression. Moreover, MDM2 is vitally involved in modifying the tumor immune microenvironment (TIME) as well as in influencing immune cells, eventually facilitating immune evasion and tolerance. Encouragingly, various MDM2 inhibitors have exhibited efficacy in relieving the TIME suppression caused by MDM2. These results demonstrate the prospects for breakthroughs in combination therapy using MDM2 inhibitors and anticancer immunotherapy.

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在恶性肿瘤中靶向 MDM2 是克服抗癌免疫疗法耐药性的一种前景广阔的策略。
通过各种胰腺癌研究,MDM2已被确定为一种生物标志物,表明接受免疫检查点抑制剂(ICI)治疗的不同恶性肿瘤患者预后不佳。具体来说,MDM2扩增的患者在接受抗癌免疫疗法后容易发展为高进展性疾病(HPD),从而对生存率产生明显的有害影响。MDM2 的作用机制涉及其在恶性肿瘤发展过程中作为癌基因的作用,MDM2 可促进转移和肿瘤细胞增殖,从而间接导致疾病进展。此外,MDM2 还参与改变肿瘤免疫微环境(TIME),并影响免疫细胞,最终促进免疫逃避和耐受。令人鼓舞的是,各种 MDM2 抑制剂在缓解 MDM2 导致的 TIME 抑制方面表现出了疗效。这些结果表明,利用 MDM2 抑制剂和抗癌免疫疗法进行联合治疗有望取得突破性进展。
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来源期刊
Journal of Biomedical Science
Journal of Biomedical Science 医学-医学:研究与实验
CiteScore
18.50
自引率
0.90%
发文量
95
审稿时长
1 months
期刊介绍: The Journal of Biomedical Science is an open access, peer-reviewed journal that focuses on fundamental and molecular aspects of basic medical sciences. It emphasizes molecular studies of biomedical problems and mechanisms. The National Science and Technology Council (NSTC), Taiwan supports the journal and covers the publication costs for accepted articles. The journal aims to provide an international platform for interdisciplinary discussions and contribute to the advancement of medicine. It benefits both readers and authors by accelerating the dissemination of research information and providing maximum access to scholarly communication. All articles published in the Journal of Biomedical Science are included in various databases such as Biological Abstracts, BIOSIS, CABI, CAS, Citebase, Current contents, DOAJ, Embase, EmBiology, and Global Health, among others.
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