Despite the acceptable safety, modulation of Notch signaling, and decreased pool of stem-like CD133+ cells, some patients experienced tumor recurrence associated with upregulation of key mesenchymal genes and VEGF-dependent angiogenic factors; moreover, the efficient Notch signaling inhibition was observed in tumors with disrupted blood-brain barrier (BBB) (NCT01119599, Table 1) [390]. The gene discussed is VEGFA; the disease is neoplasm.