Making use of the shRNA mediated knockdown of NOTCH1 we provide one possible explanation for those conflicting results: Although downregulation of NOTCH1 led to a depletion of the perivascular cell population, reduced tumor growth and reduced therapy resistance of cells in the PVN in line with previous reports7,26,44,45, it also induced TM- and network formation, thereby rendering the growth-deficient tumors virtually unsusceptible for the cytotoxic effects of radiotherapy. Here, NOTCH1 is linked to neoplasm.