The spread of cancer is a major cause of mortality and morbidity throughout Europe and beyond. As the growth of solid tumours is dependent on the formation of a neovascular supply, inhibition of tumour-induced neoangiogenesis represents an actively pursued strategy to treat human cancers. Current anti-angiogenic therapies are, however, hampered by the onset of resistance through upregulation of additional angiogenesis factors. Therefore, the identification and study of these alternative neo-angiogenesis regulators as therapeutic targets is currently of key interest. Apelin is a potent angiogenic factor frequently found upregulated in cancer. However, the in vivo pathophysiological relevance of apelin function in cancer has not been addressed so far.In this proposal, we intend to study apelin inhibition and function in spontaneous cancer models. We will take a multidisciplinary and entirely in vivo approach that will combine the power of mouse genetics with state-of-the-art analysis techniques. We will evaluate in parallel the function of apelin in cancer and the highly promising effectiveness of apelin inhibition as a therapeutic cancer target either alone or in a combined anti-angiogenesis therapy.The relevance of de novo formation of lymphatic vessels in the progression of cancer has only recently been recognized. Using state-of-the-art techniques we will extend our studies by not only assessing the in vivo role of apelin in angiogenesis but also its involvement in lymphangiogenesis. Taken together, we believe that this project will shed new light on the role and function of a novel factor that regulates vessel formation in cancer and validate its potential as therapeutic target. If successful, our in vivo multidisciplinary study will open a new avenue for the treatment of resistant cancer cases and for the development of combinatorial anti-cancer therapies with higher efficiency and a reduced incidence of resistance formation.