Notch receptor regulation: mechanism and new therapeutic approaches

This thesis describes research into the basal mechanisms underlying Notch signalling, with the idea of translating these findings into new therapeutic possibilities. Notch signalling plays an important role both during the development of the embryo and during the maintenance of various tissues afterwards.

Mammals have four different Notch receptors (Notch 1–4) and signalling is activated when Notch receptors in the cell wall interact with ligands on adjacent cells. With cancer often comes increased Notch signalling, amongst other things as a result of mutations. This leads to ligand-independent Notch signalling; in Notch 1, for example, this commonly occurs with acute lymphatic leukaemia. We have found a new way to inhibit the growth of these leukemic cancer cells and thereby also of tumours in mice by using a safe drug that is already used for other applications. Contrary to what we initially thought, these effects do not appear to be dependent on Notch signalling.