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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
Summary
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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