Treating cancer by draining its fuel tank

Mitochondria fuelled by related proteins are key to promoting the proliferative expansion and survival of cancer stem cells. Draining their fuel could form the basis of new ways of treating the disease.

Cancer stem cells are hard to eradicate: their post-treatment survival drives tumour recurrence, the systematic spread of the disease and treatment failure. Scientists at the University of Manchester investigated breast cancer stem cells grown in the lab, specifically the role of mitochondria. Their research โ€“ published in Oncotarget โ€“ revealed that these powerhouses are especially important for the proliferative growth of tumour initiating cells or stem cells, which then promotes treatment resistance.

Sixty-two mitochondrial-related proteins showed significantly increased levels in the cultured cells. Ketone and L-lactate in particular, appeared to be critical, accelerating the growth of tumours.

โ€œEssentially mitochondria are the โ€˜enginesโ€™ of cancer stem cells and ketone and L-lactate are the high octane fuels, which promote cancer growth,โ€ said Professor Michael P. Lisanti, Director of the Breakthrough Breast Cancer Unit and research leader.

โ€œThis is one of the first times that the actions of mitochondria in cancer stem cells have been fully appreciated and the results suggest new ways in which we can drain the fuel tank โ€“ restricting cancerโ€™s ability to come back after treatment.โ€

Trials are already underway using MCT inhibitors, which also targets cancer cellsโ€™ mitochondrial, and researchers believe that it could open up new avenues of treatment if successful.

โ€œTargeting the mitochondria is difficult because of potential side effects, but, if these trials prove successful, then it represents an exciting new way to treat a large number of different cancer types,โ€ said Senior Lecturer Dr Federica Sotgia, who also led the study.

โ€œBlocking cancer cellsโ€™ ability to generate the energy they need to grow and divide is an exciting new avenue for future cancer treatments,โ€ said Nell Barrie, senior science information manager at Cancer Research UK. โ€œThis research suggests that MCT inhibitors may be particularly effective against breast cancer stem cells that can resist other treatments, and could prevent the cancer from coming back โ€“ but further work is needed to find out if these types of drug can help patients.โ€

Mitochondria as new therapeutic targets for eradicating cancer stem cells: Quantitative proteomics and functional validation via MCT1/2 inhibition

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