Like many other rare diseases, investments needed for the development of drugs designed against VMs are higher than the possible profit from the markets, and therefore, it is unlikely that VMs will attract sufficient interest from pharmaceutical companies. Pathways upregulated in VMs, especially PI3K/Akt and MAPK, are extensively studied major culprits in cancer, and many experimental and clinically approved drugs targeting these pathways exist , thus making drug repurposing a logical strategy to develop Pharmacotherapy for VMs (Table 3). Direct targeting of the chronically activated TIE2 or PIK3CA kinases using specific inhibitors to stop the pathological signalling should yield the best response. Unfortunately, drug compounds specifically inhibiting TIE2 or PIK3CA have not yet reached the clinic in any indication