Two New Mechanisms Found For Disputed Anticancer Agent

Researchers find that ONC201, formerly known as TIC10, an anticancer agent whose patent is in dispute (C&EN, May 26, 2014, page 7), has additional mechanisms of action besides the one that led to its discovery. ONC201 was identified in a screen for compounds that kill cancer cells selectively by boosting expression of a gene called TRAIL (Sci. Transl. Med. 2013, DOI: 10.1126/scitranslmed.3004828). Oncoceutics, which originally patented it with the wrong chemical structure, is studying the drug in clinical trials for various cancers. Scripps Research Institute California, which discovered the error and applied for a patent on the correct structure, continues to pursue its claim. Now, Wafik S. El-Deiry of Penn State College of Medicine and R. Eric Davis and Michael Andreeff of the University of Texas MD Anderson Cancer Center and coworkers find that ONC201 also has two other mechanisms that cause cancer cells to self-destruct (Sci. Signal. 2016, DOI: 10.1126/scisignal.aac4374 and 10.1126/scisignal.aac4380). The mechanisms differ in solid tumors and blood cancers, but both boost cellular stress responses by increasing expression of the transcription factor AT4. The findings could aid clinical development of the drug, regardless of how the dispute is settled.