ArticleClinical and translational medicine2025
Targeting the MDK/c-Myc complex to overcome temozolomide resistance in glioma.
Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Systems biology of Wnt signaling in glioma chemotherapy resistance: Integrating multi-omics mechanisms and emerging therapeutic vulnerabilities (Review).Oncology letters · 2026Review
- Decoding and Overcoming Temozolomide Resistance Through CRISPR/Cas Technologies.Molecular diagnosis & therapy · 2026Review
- Micheliolide and ACT001 as Covalent Modulators of Inflammation-Redox-Metabolism Networks in CNS Disorders: An Evidence-Stratified Review of Mechanisms and Translational Challenges.Drug design, development and therapy · 2026Review
- Targeting the MDK/c-Myc complex to overcome temozolomide resistance in glioma.Clinical and translational medicine · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundTemozolomide (TMZ), which is an alkylating agent, is the standard chemotherapeutic drug used for glioma treatment. However, the development of resistance to TMZ limits its efficacy. Thus, identifying novel therapeutic targets is necessary.
methodsIn this study, the levels of midkine (MDK) and c-Myc expression in glioma patient samples downloaded from TCGA were analyzed. Their interactions were also demonstrated through microthermometry and immunocoprecipitation. Furthermore, proteomics technology and Western blot showed that MDK interacted with c-Myc and influenced its ubiquitination, thereby activating a prosurvival signalling pathway and epithelial-mesenchymal transition mechanism, which contributed to TMZ resistance. To target the MDK/c-Myc complex, we screened for a small-molecule inhibitor (ACT001) that specifically disrupts the interaction between MDK and c-Myc. Treatment with ACT001 greatly sensitized TMZ-resistant glioma cells to TMZ, promoting cell death and inhibiting cell proliferation. Moreover, combination therapy with ACT001 and TMZ showed synergistic effects that inhibit tumour growth in glioma xenograft models and glioma in situ models.
resultsACT001 facilitated the degradation of c-Myc by focusing on the MDK/c-Myc complex and controlled the Wnt/β-catenin signalling pathway via MDK, ultimately halting the advancement of glioma. When combined with TMZ, ACT001 showed good therapeutic potential for the treatment of glioma.
conclusionFocusing on the MDK/c-Myc complex could be an effective approach to combat resistance to TMZ in glioma. Therapy with ACT001 may be a novel approach to improve the efficacy of TMZ-based chemotherapy in patients with glioma. Further preclinical and clinical studies are warranted to validate the therapeutic potential of targeting the MDK/c-Myc complex in glioma treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.