Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for Metabolic Cancer Therapy

Figure 1

Lonidamine and DON targets and the rational for their combined use. (1) Glucose and glutamine are the key circulating nutrients for proliferating cells. (2) Glycolysis and glutaminolysis are cancer hallmarks. (3) Major oncogenes such as K-ras and c-myc simultaneously regulate glycolysis and glutaminolysis. (4) Cancer cells are primarily glycolytic or glutaminolytic depending upon genetic mutational landscape. (5) Cancer cells are metabolically plastic; hence they can rewire their metabolism upon nutrient availability among other factors. (6) Glycolytic and glutaminolytic inhibitors have antitumor effects on their own. (7) It is expected that upon pharmacological inhibition of glycolysis cells would survive by increasing glutaminolysis and vice versa. (8) Preclinical studies show that the combination of lonidamine and DON results in higher inhibitory effect as compared to each agent by separate. (9) Lonidamine and DON are safe drugs which have been tested in cancer patients.