When compared to normal cells, cancer cells are characterized by unrestrained growth and proliferation, which are sustained by an increased uptake, biosynthesis or catabolism of crucial metabolites, including glucose, amino acids, nucleotides and fatty acids.
The reprogramming of cellular metabolism is essential for the production of energy units, cellular biomass (including DNA, proteins and lipid macromolecules) and for the balance of redox status in cancer cells.
Owing to their specific metabolic requirements, cancer cells are more sensitive to some metabolic perturbations, including nutrient deprivation and the inhibition of specific metabolic enzymes, when compared to normal cells.
Vernieri's lab investigates mechanisms responsible for tumor cell adaptation to different types of metabolic stress, including amino acid deprivation and pharmacological treatments that target specific metabolic pathways.
Understanding how cancer cells adapt to the modulation of extracellular metabolites or metabolic pathways that sustain their growth and proliferation might provide valuable information to improve the efficacy of nutrient-restricted interventions, such as cyclic fasting and fasting-mimicking diets (FMDs), which are being explored in ongoing clinical trials.
In parallel, identifying mechanisms of tumor cell resistance to inhibitors of specific metabolic enzymes, such as the oxidative phosphorylation (OXPHOS) inhibitor metformin or the glutaminase 1 inhibitor CB-839, will suggest new strategies to combine these experimental treatments with established anticancer treatments.
The following are the main research lines of the group: