Tumour cells can adapt to sustained hypoxia through coordinated and complex intracellular signalling responses, resulting in several VEGF- and PDGF-independent proangiogenic factors, such as EGFR, PIGF, FGF2, erythropoietin (EPO), TGF-α, ΙL-6, IL-8, which induce acquired resistance and therapy failure, most importantly, activation of the HIF pathway [153]. The gene discussed is PIGF; the disease is neoplasm.