Towards a more rational use of metabolism-targeting drugs as anticancer treatments

Metabolic plasticity in cancer cells makes very challenging the use of metabolism-targeting agents as monotherapy due to resistance establishment. Moreover, the use of these drugs as anticancer treatments will not only affect cancer cells, but also immune cells in the tumor microenvironment and thereby might abrogate the beneficial effects of immunotherapy. In the first part of our work, we report that exposure to 3-bromopyruvate, a glycolysis inhibitor, renders cancer cells vulnerable to the blockade of monocarboxylate transporter 4 activity, which prevents resistant cells to growth. In the second part of this thesis, we show that acute treatment of activated T cells with fatty acid oxidation inhibitor leads to an increase of their proliferation in vitro, and to higher cytotoxic capacities towards melanoma cancer cells. Altogether our data offer metabolism-targeting therapeutic strategies to overcome resistance from plastic cancer cells and to potentiate benefits of immunotherapies.