The Notch pathway has been implicated in CRC tumors resistant to bevacizumab (anti-VEGF) and regorafenib (inhibitor of multiple kinases including VEGFR, PDGF, TIE-2 and FGF), suggesting the cross-talk of Notch with other pathways for tumor cell survival and proliferation and serving as a potential driver triggering resistance to anti-EGFR and anti-VEGF therapy63. The gene discussed is KDR; the disease is colorectal carcinoma.