Therapeutics: Notch 1 (NOTCH1); glutaminase (GLS); phosphatase and tensin homolog deleted on chromosome ten (PTEN; MMAC1; TEP1)

In vitro and mouse studies suggest combined inhibition of NOTCH1 and autophagy or GLS could help treat NOTCH-mutant, PTEN-expressing T cell-ALL (T-ALL). In a mouse model of NOTCH1 mutation-driven, PTEN-expressing T-ALL, a NOTCH1 inhibitor and knockout of genes required for autophagy decreased tumor load and increased survival compared with the NOTCH1 inhibitor alone and normal autophagic gene expression. Also in the mouse model of T-ALL, a NOTCH1 inhibitor and a GLS inhibitor decreased tumor burden compared with either agent alone. Next steps could include testing the two combinations in additional T-ALL models.

Calithera Biosciences Inc. has the GLS inhibitor CB-839 in Phase I testing to treat leukemia, hematologic malignancies and solid tumors...