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May 6, 2026CellsOpen Access

MDM2 Drives Proteasome Inhibitor Resistance and Represents a TP53-Independent Therapeutic Vulnerability in Multiple Myeloma

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Authors

MLMaria LabradorUnited Nations Industrial Development OrganizationSCSara CozzubboUnited Nations Industrial Development OrganizationMPM. PorroUnited Nations Industrial Development Organization

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Implication

Experiments reveal MDM2 drives proteasome inhibitor resistance in multiple myeloma, indicating a new treatment approach for TP53-deficient cases.

Key Points

  • This research aims to elucidate the role of MDM2 in proteasome inhibitor resistance in multiple myeloma.
  • Performed gain-of-function CRISPR activation and pharmacological screening.
  • Identified MDM2 as a modulator of proteasome inhibitor response.
  • Utilized pharmacologic inhibition of MDM2 and examined effects on multiple myeloma cell lines.
  • MDM2 transactivation supports multiple myeloma cell survival after exposure to carfilzomib.
  • Inhibition of MDM2 combined with carfilzomib enhanced sensitivity in proteasome inhibitor-resistant cell lines.
  • Combination therapy remained effective in primary patient samples, including TP53-deficient cases.

Cite This Study

Labrador et al. (2026) studied this question.

synapsesocial.com/papers/69fa8eca04f884e66b5311c0https://doi.org/10.3390/cells15090831
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Activity of PROTAC MDM2 degrader in primary leukemia cells and PDX models2026 · 1 citations
  2. 2Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer2023 · 98 citations
  3. 3Inhibition of the MDM2 E3 Ligase Induces Apoptosis and Autophagy in Wild-Type and Mutant p53 Models of Multiple Myeloma, and Acts Synergistically with ABT-7372014 · 31 citations
  4. 4Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines2023 · 11 citations
  5. 5Mdm2 Binds to Nbs1 at Sites of DNA Damage and Regulates Double Strand Break Repair2005 · 130 citations