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Eli Lilly and CNIO are collaborating on the identification and validation of novel targets in cancer immuno-metabolism. Our Section is funded through a research contract with Eli Lilly and focuses on the identification of small molecular weight molecules that regulate the metabolism of malignant cells, with the objective of killing them, either directly, acting synergistically with other anti-tumour agents, or activating the anti-tumour immune response. Exploring how to better target these mechanisms would lead to better and more efficient therapeutic options.
A combination of in vitro and in vivo approaches is being utilized to obtain a complete understanding of the metabolic reprogramming regulated by oncogenes like RAS, as well as the characterisation of the metabolic status of tumours. For this purpose, we have developed a series of biochemical and cell-based assays exploiting advanced techniques such as extracellular flux analysis (Seahorse technology), NMR and metabolomics. Finally, each target goes through an in vivo validation process using xenografts, allografts and mouse models developed at the CNIO that includes the use of non-invasive in vivo imaging technologies, as well as the immune histochemical characterisation of tumours for different metabolic, immune and tumour-specific markers. The final step is the validation in human samples from healthy donors or patients using PBMCs or tumour tissue arrays.