Cells electric charge analyses define specific properties for cancer cells activity.

The surface electrical charge of cells is conditioned by the ionic medium in which they are immersed. This charge is specific for each cell type and is especially important in tumour cells because it determines their state of aggregation and their adhesion in the different organs. This study analyses the variations in surface charge of cells when pH, electrolytes, and their concentration are modified. The modification of these factors leads to changes in the surface charge of tumour cells; therefore, their states of aggregation and behaviour can be modified. This may even have a use in the prognosis and treatment of various tumours. Some studies conclude that the activity associated with the glycolysis process is accompanied by a change in the surface charge of cells. Notably, there is a high rate of glycolysis in tumours. Our results show that surface charge of cells strongly depends on nature of ionic medium in which they are found, with the valence of the majority ion being the most important factor. When ionic strength was high, the charge decreased dramatically. On the other hand, charge becomes zero or positive in an acidic pH, while in a basic pH, the negative charge increases.

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.

Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.