Notch one for activating NOTCH

Multiple studies in recent years have called into question the use of NOTCH inhibitors to treat cancer because of an increased risk of endothelial cell tumors seen in animal models.¹ Now, researchers at Vanderbilt University have additional mechanistic evidence for this and have shown that downregulation of NOTCH signaling in fact helps tumors evade the immune system.² Instead of blocking the pathway, the Vanderbilt team thinks restoring the signaling pathway should help treat some malignancies.

In a paper published in Cancer Research, David Carbone and colleagues showed that some cancers are able to suppress T cell-mediated immunity by dampening NOTCH signaling. The team then found that restoring the pathway with a NOTCH-activating ligand called delta-like 1 (DLL1) restored immune function and decreased tumor growth...