Our research is focused on Pancreatic Ductal Adenocarcinoma (PDAC), one of the deadliest tumours nowadays. PDAC is an extremely lethal disease due to, among other factors, its high chemo-resistance and the lack of effective therapies. Indeed, due to the lack of specificity of early symptoms, 80-90% of the patient cohort is diagnosed at advanced/metastatic stages, and virtually all patients die within 12 months. Thus, new therapeutic concepts are urgently needed.
PDAC tumours are organised hierarchically with cells featuring stem-like properties (cancer stem cells, CSCs) at the origin of tumour heterogeneity. These cells are chemoresistant and highly tumorigenic, representing the main source of disease relapse and metastasis. For that reason, eliminating CSCs might be the only efficient strategy to ensure long-term survival in patients.
As part of our pioneer research in the field of pancreatic CSCs metabolism, we recently discovered that these cells are particularly sensitive to drugs targeting mitochondrial metabolism, such as the antidiabetic drug metformin. One of the main research lines on the group explores new ways of targeting CSC mitochondria, by blocking different pathways that control their integrity and lifecycle.
Mitochondrial metabolism allows CSCs to use a wide range of substrates, including lipids. In fact, lipid metabolism plays an essential role for CSC functionality in other tumour types, representing a clear target to eliminate these tumorigenic cells. In this sense, we are exploring the role of lipid uptake and storage as well as FA metabolism for tumour progression and metastasis, with the ultimate aim of identifying and validating most effective CSC-targeting strategies with great translational potential.