Research And Grants

Preclinical evaluation of TP-0184 in an autochthonous mouse model of DIPG/DMG

Evaluation of new cancer drugs, and determining which models best predict whether the new cancer drug will benefit children with DMG/DIPG is unclear.   DMG/DIPG tumor cells have complex interactions with cell types normally found in the brain. Therefore, new therapies must be evaluated in animal models where DMG/DIPG tumor cells arise in the brainstem.  There are several types of DMG/DIPG models:

1. Using cells from patients with DMG/DIPG.  This model requires mice without an immune system.

2. Introducing DMG/DIPG specific genetic alterations into normal mouse brainstem cells. This model has more heterogeneity.

3. Using tumor cells from model #2 but injecting the tumor cells into a new mouse with a normal immune system to minimize heterogeneity.

TP-0184 is a drug with multiple targets, such a cell surface receptor called ACVR1 (overactive in 25% of DMG/DIPG tumors) and two other targets JAK2 and ALK5.   These targets or the molecules that activate them are expressed in immune cells, so evaluation in models with a normal immune system is critical.  Therefore, we will evaluate TP-0184 in models #2 and #3.  We expect that TP-0184 will work in model #3 but not #2 and we will examine mechanisms of resistance to model#3