Chloroquine has therapeutic effect in IDH-mutant U87 mouse model

This was an orthotopic mouse model: U87 GBM cells with either wild-type IDH or genetically engineered to contain the IDH1 R132H mutation were injected into brains of nude (immunodeficient) mice. Chloroquine was injected intraperitoneally.

According to this study, 2-hydroxyglutarate produced by the mutant IDH1 enzyme leads to endoplasmic reticulum (ER) stress, autophagy of the endoplasmic reticulum, and reduced biosynthesis of membrane phospholipids (as the ER is the site of phospholipid synthesis). Inhibiting autophagy with chloroquine triggered apoptosis (programmed cell death).

Chloroquine-treated IDH1-mutant U87 tumors had increased caspase activity (a marker of apoptosis), while the IDH1 wild-type U87 tumors had no increase in caspase activity with chloroquine treatment.

Study title:
2-hydroxyglutarate-mediated autophagy of the endoplasmic reticulum leads to an unusual downregulation of phospholipid biosynthesis in mutant IDH1 gliomas
Pubmed link

I've uploaded the full study to the Library (Folder 2 Therapies - preclinical -> Chloroquine)