MetabRes_CESPU_2017: Unraveling the role of cell metabolism and tumor microenvironment in the molecular mechanisms of resistance in cancer.
admin-cespu
Principal Investigator:
Odília dos Anjos Pimenta Marques de Queirós (odilia.queiros@iucs.cespu.pt)
Leader Institution:
CESPU
Research Team:
Andrea Cunha, Diana Valente, Joana Vieira, Ricardo Dinis-Oliveira, Fátima Baltazar
Funding entity:
CESPU
Budget:
6.000,00 €
Period covered:
2017-2018
Abstract:
Cancer is characterized by an uncontrolled cellular growth, implying a metabolic reprogramming, in which glycolysis is preferentially used, leading to microenvironment acidification. 3-bromopyruvate (3BP), dichloroacetate (DCA) and 2-deoxyglucose (2DG) inhibit cancer cell energy metabolism and modify the microenvironment, affecting the proteins involved in the resistance to chemotherapy. Therefore, we will elucidate the common mechanisms of resistance to 3BP, DCA and 2DG. First, we will assess the sensitivity of a lung cancer model to 3BP, DCA and 2DG and characterize their effect on viability, proliferation, migration, invasion and death. We will study the mechanism by which 3BP, DCA and 2DG can potentiate the action of conventional antitumor drugs and, thus, the possibility of being used in a combination therapy. Then, we will elucidate the molecular mechanisms involved in 3BP, DCA and 2DG action in tumor cells, by constructing cell lines resistant to these compounds.
Cancer is characterized by an uncontrolled cellular growth, implying a metabolic reprogramming, in which glycolysis is preferentially used, leading to microenvironment acidification. 3-bromopyruvate (3BP), dichloroacetate (DCA) and 2-deoxyglucose (2DG) inhibit cancer cell energy metabolism and modify the microenvironment, affecting the proteins involved in the resistance to chemotherapy. Therefore, we will elucidate the common mechanisms of resistance to 3BP, DCA and 2DG. First, we will assess the sensitivity of a lung cancer model to 3BP, DCA and 2DG and characterize their effect on viability, proliferation, migration, invasion and death. We will study the mechanism by which 3BP, DCA and 2DG can potentiate the action of conventional antitumor drugs and, thus, the possibility of being used in a combination therapy. Then, we will elucidate the molecular mechanisms involved in 3BP, DCA and 2DG action in tumor cells, by constructing cell lines resistant to these compounds.
Project area: