MAP2K7 and malignant peripheral nerve sheath tumor: Though sensitivity is variable, we report nirogacestat, which blocks γ-secretase processing and activation of NOTCH proteins, is capable of inhibiting the growth of MPNST cells and shows strong synergy with MEK inhibition, a common class of drugs investigated in MPNSTs.61,62 There is promising work with anti-angiogenesis drugs which block ligand binding to NOTCH receptors (brontictuzumab) and pan-NOTCH inhibitors (crenigacestat).63 We predicted NOTCH GOF lines would have higher nirogacestat IC50 than luciferase control lines.