Selection of the best HIT in the prevention of anti-angiogenic resistance and validation of a biomarker involved

Identifier:  TFG:2175

Handle: https://hdl.handle.net/20.500.11797/TFG2175

Authors:  Babiloni Simón, Sonia

Abstract:
Selection of the best HIT in the prevention of anti-angiogenic resistance and validation of biomarkers involved. Tumor growth and metastasis relies on angiogenesis, the formation of new blood vessels from pre-existing vascular beds, in order to receive an adequate supply of oxygen and nutrients. Therefore, targeting tumor angiogenesis has become of high clinical relevance. Nevertheless, resistance observed in several tumor types through alternative angiogenic “escape” pathways contributes to restoration of tumor growth. Our group in the laboratory recently described a new mechanism of tumor adaptation and relapse based on nucleoside catabolism that could be useful to prevent anti-angiogenic resistance. Has been done the target validation and the HIT identification through a Computational Drug Discovery analyzing our new therapeutic target, this analysis threw relevant scaffolds from these we analyzed different libraries and we filtered the structures until we had three possible HIT candidates. In this study was performed the in vitro evaluation to determine the IC50 of the two best HITs in RCC, lung and pancreatic adenocarcinoma cell lines. Moreover, using the best candidate we perform the in vivo evaluation of initial toxicity and effectivity. In parallel, another molecule implicated on nucleoside catabolism was validated as a biomarker of resistance to anti-angiogenic treatment.