ONC201: Stressing tumors to death

Sci Signal. 2016 Feb 16;9(415):fs1. doi: 10.1126/scisignal.aad7955.


The small molecule ONC201 was identified in a screen for compounds that would induce expression of the gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in tumors and thus cause an autocrine- or paracrine-induced death in tumor cells. Two Research Articles in this issue of Science Signaling by Ishizawa et al. and Kline et al. describe how ONC201 can also trigger cytotoxicity by inducing a stress response. The mechanisms of the stress response induced differ between hematological malignancies and solid tumors, highlighting the complexity of ONC201-induced toxicity and raising intriguing issues of tissue-specific pathways activated by the drug.

Publication types

  • Research Support, N.I.H., Intramural
  • Review
  • Comment

MeSH terms

  • Hematologic Neoplasms
  • Humans
  • Neoplasms*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*


  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand