Tumor microenvironment involvement in the metabolic reprogramming induced by the PDK inhibitor dichloroacetate

The objective of the thesis is to explore the influence of different aspects of the tumor microenvironment (TME) on the anti-cancer response to dichloroacetate (DCA). DCA modulates tumor metabolism by stopping the overconsumption of glucose, which may reduce tumor growth. The increased consumption of glucose by cancer cells leads to acidification of the extracellular environment and initiates angiogenesis, the extension of blood vessels to supply the tumor. However, little information is known on how the tumor adapts its metabolism to extracellular acidosis and whether DCA affects tumor angiogenesis. Using cancer cell lines adapted to acidic pH, we demonstrated that the metabolic changes acquired following adaptation to acidic pH render the cells more sensitive to DCA. By working with endothelial cells (ECs) which are the cells that constitute blood vessels, we found that DCA had a direct effect on these cells by reducing their activation. Our results emphasize the importance of taking into account the influence of MET in the response to DCA in order to better target tumors that would respond to this treatment.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202