A research study has revealed a new signaling pathway in which cancer cells die from being deprived of glucose. The knowledge gained from this discovery could be used as a therapy to target specific tumor types or to prevent cell death in non-cancerous cells. The study findings were published in Science Signaling.
It’s well established that some rapidly growing cancer cells require more sugar than normal cells. Drug therapies that reduce sugar in order to stop cancer from spreading have been tried but without much success. Some cancer cells don’t require excess sugar and depleting sugar from glucose-dependent cell types appears to only slow their growth instead of stopping cancer progression. The study showed that glucose deprivation triggers a signaling pathway in cancer cells comprising an influx of calcium ions into the cell which activates CAMK1 kinase, ultimately leading to cell death through the RIPK1 kinase pathway. Importantly, the study also showed that the nonmetabolizable glucose analog and glyocolytic inhibitor, 2-deoxy-D-glucose (2-DG), prevented cell death. The analog appears to stop plasma membrane depolarization so calcium ions cannot flood the cell and trigger the cell death signaling cascade.
The research team successfully demonstrated that the combination approach of glucose inhibition and increased intracellular calcium levels killed cancer cells without harming normal cells. The hope is that this dual method can be used as a novel treatment approach for certain cancer types. A patent application has been submitted for “A potential combination therapy using an inhibitor of glucose transport and an intracellular calcium inducer to target cancer metabolism.”