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Nutritional strategies and bioactive compounds to target lipid metabolism alterations in cancer: Platform of Patient derived Paired Organoids for Precision Nutrition

19th national competition for scientific and technical research

Food security and biotechnology

Senior Researcher : Ana Ramírez Molina

Research Centre or Institution : Instituto Madrileño de Estudios Avanzados (IMDEA) en Alimentación. Madrid.

Abstract

The objective of this project is the design of nutritional strategies based on bioactive extracts targeting alterations in lipid metabolism in cancer. To do this, the nutritional and metabolic status of patients is taken into account, integrating genomic and lifestyle data. Throughout the project, biomarkers associated with metabolic status have been evaluated (1). It has also been proposed that metabolic health (MH) together with a lipid genetic risk score predicts survival of patients with small cell lung cancer of great clinical value (2). In line with these results, we have defined a highly specific biomarker for early-onset colorectal cancer that integrates the involvement of metabolic pathways as well as gender disparities (Fernández et al., submitted, (3)). In addition, we are analyzing the role of individual MH in CRC growth, studying the impact of various parameters on the growth of CRC spheroids, finding that is significantly modulated in the presence of certain human plasmas that share a particular genetic and lipid profile, and specific dietary patterns. (Cruz-Gil et al., in preparation).
Finally, metabolic phenotypes associated with the state of obesity have been studied, analyzing anthropometric and clinical parameters in healthy volunteers, and studying associations with single nucleotide polymorphisms (SNPs) in metabolic genes associated with cell signaling by nutrients (mTOR pathway) (4). In addition, in a recent study in healthy volunteers it has been shown that fasting could be protecting against the toxicity associated with chemotherapy (5). Recently, we have identified lipid metabolism genes that are involved in the differential spread of CRC tumors to the liver and/or lung that can be modulated by nutritional interventions, including bioactive compounds and nutraceuticals (6). Besides, more than 20 natural extracts approved for human consumption have been screened to assess their effects in controlling metabolic stress and inflammation associated with chronic diseases, including cancer (7–9). In a preclinical model of obesity, the beneficial effect of two extracts has been demonstrated, identifying their molecular mechanisms of action, for their personalized application in cancer patients (10), (Reguero et al. 2023, in preparation). Finally, the epigenetic regulation of different compounds has also been studied for their targeted use in cancer treatment (11). Based on previous results of the formulation based on rosemary extract and alkylglycerols (Lipchronic-PCT/ES2017/070263) (9) (12), a clinical trial has been carried out with patients with CRC, breast cancer, and lung cancer. Preliminary analyzes suggest that Lipchronic has a direct effect on immune system mediators with possible effects in controlling tumor progression (OncoVINF-ClinicalTrials.govIdentifier-NCT05080920 study).

 

Scientific Production
 
Magazine Articles 7
Communications at national conferences 5
Communications at international conferences 2

 

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