The physiological basis for bevacizumab- and sorafenib-induced HT and HFSR is currently unknown although they most likely originate from the activity of these drugs altering signaling through several targets (i.e., VEGF, Raf-1, wild-type B-Raf, mutant b-raf V599E, VEGFR2, VEGFR3, PDGFR-β, Flt3, c-KIT and p38) [19,20]; recent data suggests that the VEGF pathway directly contributes [6,7]. The gene discussed is FLT4; the disease is hematocrit.