Eli Lilly and CNIO are collaborating on the identification and validation of novel targets in cancer immunometabolism. Our Section is funded through a research contract with Eli Lilly and focuses on identifying small molecular weight molecules that regulate the metabolism of malignant cells, with the objective of killing them either directly, by acting synergistically with other antitumour agents, or indirectly by activating the antitumour 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 utilised to obtain a complete understanding of tumour metabolic reprogramming and the antitumour response. For this purpose, we developed a series of biochemical and cell-based assays exploiting advanced techniques such as extracellular flux analysis (Seahorse technology), nuclear magnetic resonance, metabolomics and immunophenotyping. Finally, each target goes through an in vivo validation process using xenografts, allografts and mouse models developed at the CNIO. This includes the use of non-invasive in vivo imaging technologies, and immune histochemical characterisation of tumours for different metabolic, immune and tumour markers. The final step is the validation in human samples using tumour tissue arrays.