High-glycolytic cancers and their interplay with the body's glucose demand and supply cycle

Abstract

Many difficult-to-treat solid cancer tumours and metastases have high-glucose uptake, usually under hypoxic conditions. Hypoxic tumours suppress the immune system and are insensitive to traditional chemoradiotherapies. The only therapy usually available is surgical resection. However, with widespread metastases, surgery often becomes unviable. Surgery in itself can also result in metastasis. The need for investigating adjuvant treatments is obvious. Here we investigate whether the high-glucose uptake of hypoxic tumours could lead to such a treatment. Before any treatment can be hypothesised, it is crucial to understand how this glycolytic cancer phenotype fits in with the normal body's blood glucose cycle. The brain creates the healthy body's largest demand for blood glucose (BG) and ensures a very high level of control on in vivo supply. It is hypothesised that, through somatic evolution, high-glycolytic cancer cells opportunistically tap into this very stable energy environment. It is shown that therapies which target the glycolytic cancers' high BG needs cannot be developed without addressing the brain's energy needs. Based on this knowledge, and to initiate thinking on potential BG therapies, a first attempt is made at hypotheses for potential control of the in vivo brain demand as well as the available in vivo BG. The aim is to adversely affect primary as well as metastatic tumours without damaging brain and innocent bystander cells.