SEARCH

SEARCH BY CITATION

Dear Sir,

Polet and Feron [1] elucidate inter alia pharmacological interventions, which affect the glucose, glutamine and lactate pathways. These are important due to their putative anticancer effects. Recapitulating their therapeutic effect is unfortunately difficult by only cytotoxic means [2] due to, among others, the ‘innocent bystander effect’ [3]. Recent evidence, however, suggests that control of highly glycolytic cancer may be simpler than expected.

It was recently shown that glucose appears at the top of the cancer cell (and cancer-associated fibroblast) metabolic hierarchy [4]. Therefore, if cancer cells (and associated fibroblasts) can be deprived of glucose, the cancer cells will not only be ineffective to metabolize glutamine but will also be deprived of de novo produced lactate, fatty acids and ketone bodies [5].

Preliminary data show that carbohydrate restriction diets resulting in moderate ketosis can result in stabilization or remission of cancer [6]. Such diet-induced suppression of glucose and insulin levels might be more effective when combined with the pharmacological agents summarized by Polet and Feron [1], but this remains to be proven.

However, the mechanical, rather than chemical, control of cancer metabolism via extracorporeal blood treatment may also afford a unique therapeutic opportunity. This could be achieved by arranging lower concentrations of glucose and glutamine in the dialysate, and by selection of an appropriate dialyser membrane (for diffusion of glucose and glutamine to the dialysate) [4]. When depriving the whole body of glucose and glutamine, safe concentrations are typically 2 m mol L−1 and 1 m mol L−1, respectively [7]. Reduction of glucose and glutamine to such physiologically safe concentrations should adversely affect tumour angiogenesis [8-10].

To enhance cancer cell killing, it might be prudent to combine glucose/glutamine deprivation therapies (extracorporeal or dietetic) with pharmacotherapeutics. Also, lower concentrations of cytotoxic agents would then be required, with lower adverse effects to surrounding healthy tissue. We believe that this merits further investigation.

Conflict of interest statement

No conflict of interest was declared.

References

  1. Top of page
  2. References