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ONC201: Stressing tumors to death

Yoshimi Endo Greer1, Stanley Lipkowitz2

  • 1Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Science Signaling
|February 18, 2016
PubMed

Insights

The small molecule ONC201 induces tumor cell death by triggering a stress response. Its mechanisms of action vary between blood cancers and solid tumors, revealing tissue-specific pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce cancer cell death.
  • ONC201 is a small molecule identified for its potential to upregulate TRAIL.
  • Understanding drug-induced stress responses is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the cytotoxic mechanisms of ONC201 beyond TRAIL induction.
  • To explore the role of stress response pathways in ONC201-mediated cell death.
  • To identify potential differences in ONC201's action in various cancer types.

Main Methods:

  • Compound screening to identify TRAIL-inducing agents.
  • Analysis of cellular stress responses following ONC201 treatment.
  • Comparative studies in hematological malignancies and solid tumor models.

Main Results:

  • ONC201 triggers cytotoxicity through induced stress responses.
  • The specific stress response pathways differ between blood cancers and solid tumors.
  • This highlights tissue-specific activation of pathways by ONC201.

Conclusions:

  • ONC201 exhibits complex cytotoxicity involving stress responses.
  • Tissue-specific mechanisms underscore the need for tailored therapeutic strategies.
  • Further research into ONC201's pathways may reveal new cancer treatment avenues.

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