Related Experiment Video

Updated: May 17, 2025

An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity
07:58

An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity

Published on: May 12, 2020

6.7K

ONC201 exerts oncogenic effects beyond its mitochondria-disturbing role in neuroblastoma subsets

Jyun-Hong Jiang1,2, Yu-Han Lin2, Pei-Lin Liao1,2

  • 1Department of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital, Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan.

Journal of Molecular Medicine (Berlin, Germany)
|April 10, 2025
PubMed

Insights

ONC201 did not reduce tumor growth in animal models of non-MYCN-amplified neuroblastoma. The drug increased oncogenic markers and decreased a tumor suppressor, suggesting complex effects beyond mitochondrial targets.

Area of Science:

  • Pediatric Oncology
  • Molecular Therapeutics
  • Cancer Biology

Background:

  • Neuroblastoma (NB) presents a significant challenge in pediatric oncology.
  • ONC201, an imipridone, shows anticancer potential, particularly in MYCN-amplified NB.
  • Efficacy of ONC201 in non-MYCN-amplified NB requires further investigation.

Purpose of the Study:

  • To evaluate the efficacy of ONC201 in non-MYCN-amplified neuroblastoma models.
  • To investigate the molecular mechanisms underlying ONC201's effects in this subtype.
  • To determine if ONC201's actions are solely dependent on mitochondrial targets.

Main Methods:

  • Utilized animal models with non-MYCN-amplified NB cell lines (SK-N-AS, SK-N-FI).
  • Assessed tumor growth, neovascularization, and expression of key molecular markers (c-Myc, LGR5, ATRX).
  • Investigated effects in Rho zero (ρ0)-SK-N-AS cells to explore mitochondrial independence.

Main Results:

  • ONC201 failed to reduce tumor growth in non-MYCN-amplified NB models.
  • ONC201 induced oncogenic markers c-Myc and LGR5 while downregulating tumor suppressor ATRX.
  • ONC201 did not attenuate tumor neovascularization and showed similar molecular trends in ρ0 cells.

Conclusions:

  • ONC201 monotherapy may not be effective for neuroblastoma lacking MYCN-amplification.
  • The drug's effects involve modulation of oncogenic and tumor suppressor pathways.
  • Understanding specific molecular signatures is crucial for ONC201 treatment decisions in NB.
Keywords:
ATRXLGR5NeuroblastomaNon-MYCN-amplified cell lineONC201

More Related Videos

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens09:33

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

Published on: August 25, 2023

1.0K
Author Spotlight: Decoding Mitochondrial Aging08:48

Author Spotlight: Decoding Mitochondrial Aging

Published on: June 30, 2023

3.5K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
3.9K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.3K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.5K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
9.6K