Mechanisms proposed to drive tumor progression and metastasis in the face of VEGFR inhibition include vascular pruning leading to acute hypoxic stress, activation of alternative angiogenic pathways (e.g. signaling between the tumor stroma and cells of the immune system) and up-regulation of proangiogenic factors (e.g. FGF, PDGF), among others [38–42]. The gene discussed is KDR; the disease is neoplasm.