Related Experiment Video

Updated: Aug 18, 2026

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

Targeting the MDK/c-Myc complex to overcome temozolomide resistance in glioma

Xiaonan Xi1,2,3, Xiaojing Ding2, Qianqian Wang1,2

  • 1State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.

Clinical and Translational Medicine
|June 5, 2025
PubMed
Abstract

Insights

Targeting the midkine (MDK) and c-Myc complex with ACT001 overcomes temozolomide (TMZ) resistance in glioma. This combination therapy shows significant potential for improving glioma treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Temozolomide (TMZ) is a standard glioma treatment, but resistance limits its effectiveness.
  • Identifying novel therapeutic targets is crucial for overcoming TMZ resistance in glioma.

Purpose of the Study:

  • To investigate the role of midkine (MDK) and c-Myc in TMZ resistance in glioma.
  • To evaluate the therapeutic potential of targeting the MDK/c-Myc complex with a novel inhibitor, ACT001.

Main Methods:

  • Analyzed MDK and c-Myc expression in glioma samples from TCGA.
  • Investigated MDK-c-Myc interactions using microthermometry and immunoprecipitation.
  • Utilized proteomics and Western blot to confirm MDK's influence on c-Myc ubiquitination.
  • Screened for small-molecule inhibitors targeting the MDK/c-Myc complex, identifying ACT001.
  • Assessed ACT001 efficacy alone and in combination with TMZ in vitro and in vivo glioma models.

Main Results:

  • MDK interacts with c-Myc, influencing its ubiquitination and activating pro-survival pathways, contributing to TMZ resistance.
  • ACT001 specifically disrupts the MDK/c-Myc interaction, sensitizing resistant glioma cells to TMZ and promoting cell death.
  • Combination therapy with ACT001 and TMZ demonstrated synergistic effects in inhibiting tumor growth in preclinical models.

Conclusions:

  • Targeting the MDK/c-Myc complex is a promising strategy to overcome TMZ resistance in glioma.
  • ACT001, in combination with TMZ, shows significant therapeutic potential for glioma treatment.
  • Further studies are warranted to validate ACT001's efficacy in clinical settings.
Keywords:
ACT001MDKdrug resistancegliomaprotein complex

More Related Videos

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care12:55

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

Published on: February 16, 2015

Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing09:24

Generation of Microtumors Using 3D Human Biogel Culture System and Patient-derived Glioblastoma Cells for Kinomic Profiling and Drug Response Testing

Published on: June 9, 2016

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...