Cancer and tumor metastasis is the largest single cause of death in both, men and women, claiming over 7 million lives each year worldwide and, it is expected that by 2020 the number of dead cancer patients will grow to 10 million per year. Metastatic tumor cells utilize blood and lymphatic vessels as routes for dissemination and it is well known that lymphatic vasculature serves as a major route for tumor metastasis. Besides, lymphangiogenesis, the new lymphatic vessels formation from pre-existing ones, is pivotal for cancer cells spreading from primary sites to lymph nodes and, further, to distant tissues. Consequently, the search and identification of new tumor-induced lymphangiogenesis inhibitors and the understanding of their mechanisms of action, are a hot topic in the field of pharmacological research. In the present project, the applicant will finished the characterization of two marine compounds, toluquinol and AD0157, started during a short stay in the host institute. Preliminary results have shown that both compounds have excellent antilymphangiogenic properties in in vitro and ex vivo assays and, in the course of the present project they will be tested in in vivo models and their molecular targets will be revealed. Furthermore, other two new marine compounds will be analyzed in in vitro, ex vivo and in vivo experimental approaches. In these studies the applicant will focus in the behavior of the lymphatic endothelial tip and stalk cells, in order to shed light on their morphological and biochemical features. Hence, this project will increase significantly the acquisition of innovative knowledge on lymphangiogenesis phenomenon, on the different lymphatic endothelial tip/stalk cells features and on the cellular and molecular mechanisms of action of some natural compounds to inhibit tumor-related lymphangiogenesis. Those compounds with excellent antilymphangiogenic properties will be patented in order to be commercially exploitable as antitumor drugs.