ArticleBiomedicines2024
New Insights into Chemoresistance Mediated by Mdm2 Inhibitors: The Benefits of Targeted Therapy over Common Cytostatics.
Article in Biomedicines, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- The Managed Acquisition of Chemoresistance as an Informative Tool for Tumor Research.International journal of molecular sciences · 2025Review
- Development of Drug-resistant Cell Lines for Experimental Procedures.Journal of visualized experiments : JoVE · 2025Article
- Mechanistic Insights into the Anti-Hepatocellular Carcinoma Effects of ACY-1215: p53 Acetylation and Ubiquitination Regulation.Current issues in molecular biology · 2025Article
- Review
- Ubiquitin recruiting chimera: more than just a PROTAC.Biology direct · 2024Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The inhibition of the Mdm2-p53 protein-protein interaction is a promising strategy for anticancer therapy. However, the problem of developing secondary chemoresistance in tumors treated with such drugs has not yet been sufficiently studied. In this work, we compared the properties of a drug-resistant cell line obtained during long-term cultivation in the presence of an Mdm2 inhibitor, Nutlin-3a, with a similarly obtained line insensitive to the cytostatic drug paclitaxel. We first confirmed the higher safety levels of Mdm2 inhibitors when compared with cytostatics in terms of the development of secondary chemoresistance. We showed that Nutlin-3a affects both the targeted p53-mediated cellular machinery and the universal ABC-mediated efflux mechanism. While both targeted and general defense mechanisms are activated by the Mdm2 inhibitor, it still increases the susceptibility of tumor cells to other drugs. The results obtained indicate that the risks of developing chemoresistance under the therapy with a targeted agent are fundamentally lower than during cytotoxic therapy.
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Registered trials
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