Novel alternatives for anti-angiogenetic therapy and therapeutic angiogenesis.

Anti-angiogenic therapy and therapeutic angiogenesis have been proposed as opposite strategy for the treatment of cancer and ischemic diseases, respectively. However, both approaches do not provide long term solutions of these pathological conditions and have failed in clinical trials. Therefore, novel strategies are needed. In the current work we describe: 1) how vessels sense and re-adapt oxygen supply and, hence, perfusion in case of oxygen shortage, therefore identifying PHD2 oxygen sensor as a novel target to normalize the tumor vasculature, reduce cancer hypoxia and prevent cancer cell extravasations and dissemination; 2) anti-P1GF as a efficient and safe tool in cancer therapy that does not prune excessively pathological vessels and does not affect the normal vasculature; 3) hypoxia tolerance via inhibition of the oxygen sensor PHD1 as alternative strategy to therapeutic angiogenesis. Altogether, our findings provide new alternatives in the treatment of ischemic disorders and cancer, largely unmet medical problems to date.