Anti-angiogenic Therapy in Cancer: Downsides and New Pivots for Precision Medicine

Primary solid tumors originate close to pre-existing tissue vasculature, initially growingalong such tissue blood vessels, and this phenomenon is important for the metastaticpotential which frequently occurs in highly vascularized tissues. Unfortunately, preclinicand clinic anti-angiogenic approaches have not been very successful, and multiplefactors have been found to contribute to toxicity and tumor resistance. Moreover, tumorscan highlight intrinsic or acquired resistances, or show adaptation to the VEGF-targetedtherapies. Furthermore, different mechanisms of vascularization, activation of alternativesignaling pathways, and increased tumor aggressiveness make this context even morecomplex. On the other hand, it has to be considered that the transitional restoration ofnormal, not fenestrated, microvessels allows the drug to reach the tumor and act withthe maximum ef?ciency. However, these effects are time-limited and different, dependingon the various types of cancer, and clearly de?ne a speci?c normalization window.So, new horizons in the therapeutic approaches consist on the treatment of the tumorwith pro- (instead of anti-) angiogenic therapies, which could strengthen a network ofwell-structured blood vessels that facilitate the transport of the drug.