bims-midomi Biomed News
on MDM2 and mitochondria
Issue of 2025–07–06
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. Targeting p53 activation: Recent therapeutic advances in cancer and diabetic macular edema.
  2. Research on the mechanism of GRIM-19 affecting lung adenocarcinoma through regulating MDM2 and EMT pathways.
  1. Eur J Med Chem. 2025 Jun 27. pii: S0223-5234(25)00674-9. [Epub ahead of print]297 117909
    Targeting p53 activation: Recent therapeutic advances in cancer and diabetic macular edema.
    Zhiyi Wang, Shijie Zhang, Loïca Mélita Irakoze, Yujun Zhao.
      p53, encoded by the TP53 gene, is a critical tumor suppressor, and its pharmacological activation has been clinically validated as an effective strategy for the treatment of human malignancies. In recent years, numerous novel approaches have emerged to activate both wild-type and mutant p53, including MDM2 degraders, p53 stabilizers, gene therapies targeting TP53, and inhibitors of the MDM2-p53 protein-protein interaction. Since 2020, drug discovery efforts in these areas have advanced rapidly, leading to several notable breakthroughs. This review provides a comprehensive overview of recently reported agents that enhance p53 function, with particular emphasis on those that have progressed to clinical trials or are capable of restoring p53 activity in cancers harboring TP53 mutations. We aim to offer an up-to-date snapshot of the evolving landscape of p53-targeted therapies and to serve as a reference for future drug discovery endeavors in this important field.
    Keywords:  Degrader; Gene therapy; MDM2; Mutant p53; PROTAC; Protein-protein interaction; p53
    DOI:  https://doi.org/10.1016/j.ejmech.2025.117909
  2. Cytotechnology. 2025 Aug;77(4): 130
    Research on the mechanism of GRIM-19 affecting lung adenocarcinoma through regulating MDM2 and EMT pathways.
    Pengfei Guo, Song Zhao, Xiaoli Han, Jingtao Huang, Zongying Liang.
      Previously, there have been reports of decreased expression of GRIM-19 and increased expression of MDM2 in lung adenocarcinoma. However, the relationship between GRIM-19 and MDM2 in lung adenocarcinoma has not been reported yet. In this study, we demonstrated that GRIM-19mRNA expression was reduced in lung adenocarcinoma tissue while MDM2mRNA expression was increased. Pearson correlation coefficient analysis showed a significant correlation between GRIM-19mRNA and MDM2mRNA (r = -0.970, p < 0.001). In this study, we further detected by experiments that the overexpression of GRIM-19 lowered the expression level of MDM2 protein, suggesting that GRIM-19 may affect the occurrence and development of lung adenocarcinoma by inhibiting the expression of MDM2. Cellular functional and subcutaneous tumour formation experiments in nude mice have shown that GRIM-19 inhibits the proliferation, invasion, and migration ability of lung adenocarcinoma cells, promotes cell apoptosis, and ultimately inhibits lung adenocarcinoma development. In addition, overexpression of GRIM-19 in A549 cells resulted in significant changes in the expression of EMT-related proteins Snail, N-Cadherin, E-Cadherin, and Vimentin, indicating that GRIM-19 may inhibit the metastasis of lung adenocarcinoma cells by regulating the EMT pathway.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-025-00797-5.
    Keywords:  Adenocarcinoma of the lung; EMT; GRIM-19; MDM2
    DOI:  https://doi.org/10.1007/s10616-025-00797-5
This page is being maintained by Thomas Krichel. It was last updated on 2025‒07‒16 at 21:28.