Imipridones affect tumor bioenergetics and promote cell lineage differentiation in diffuse midline gliomas
Justyna M Przystal, Chiara Cianciolo Cosentino, Sridevi Yadavilli, Jie Zhang, Sandra Laternser, Erin R Bonner, Rachna Prasad, Adam A Dawood, Nina Lobeto, Wai Chin Chong, Matt C Biery, Carrie Myers, James M Olson, Eshini Panditharatna, Bettina Kritzer, Sulayman Mourabit, Nicholas A Vitanza, Mariella G Filbin, Geoffry N de Iuliis, Matthew D Dun, Carl Koschmann, Jason E Cain, Michael A Grotzer, Sebastian M Waszak, Sabine Mueller, Javad Nazarian
Abstract
Pediatric diffuse midline gliomas (DMGs) are incurable childhood cancers. Imipridones are chemical compounds used to treat cancers orally. The imipridone ONC201 has shown early positive effects on DMGs. However, the anticancer mechanisms of ONC201 and its derivative ONC206 have not been fully described in this type of tumor. Researchers in this study found that chemicals targeting mitochondrial metabolism and ISR activation effectively impairs DMG growth. These results further support the use of imipridone ONC201 to treat pediatric DMGs.