Figure 4

Hypothetical approach to kill cancer cells with limited glucose supply or under glucose deprivation by targeting intratumoral lactic acidosis. (a) The roles of lactic acidosis in tumors: under glucose shortage, lactic acidosis switches cancer cells from Warburg effect to economic metabolic mode, to balance glucose consumption and glucose supply; under temporary or constant glucose deprivation, lactic acidosis rescues cancer cells. Thus, converting intratumoral lactic acidosis to lactosis by a base would lead to two consequences, switching cancer cells from economic metabolic mode to Warburg effect to exhaust glucose and abolishing the protective role of lactic acidosis against glucose deprivation. (b) If the hypothesis is correct, bicarbonate injection for elevation of intratumoral pH to convert lactic acidosis to lactosis would inhibit tumor growth and enhance intratumoral necrosis. This was observed in an animal tumor model, bicarbonate converted intratumoral lactic acidosis to lactosis, accompanied with a tumor growth inhibition and enhanced intratumoral necrosis.³⁰