摘要
Treatment-resistance is common in glioblastoma(GBM)and the glioblastoma stem-like cells(GSC)from which they arise.Current treatment options are generally regarded as very poor and this arises from a poor conceptualization of the biological underpinnings of GBM/GSC and of the plasticity that these cells are capable of utilizing in response to different treatments.A number of studies indicate melatonin to have utility in the management of GBM/GSC,both per se and when adjunctive to chemotherapy.Recent work shows melatonin to be produced in mitochondria,with the mitochondrial melatonergic pathway proposed to be a crucial factor in driving the wide array of changes in intra-and inter-cellular processes,as well as receptors that can be evident in the cells of the GBM/GSC microenvironment.Variations in the enzymatic conversion of N-acetylserotonin(NAS)to melatonin may be especially important in GSC,as NAS can activate the tyrosine receptor kinase B to increase GSC survival and proliferation.Consequently,variations in the NAS/melatonin ratio may have contrasting effects on GBM/GSC survival.It is proposed that mitochondrial communication across cell types in the tumour microenvironment is strongly driven by the need to carefully control the mitochondrial melatonergic pathways across cell types,with a number of intra-and inter-cellular processes occurring as a consequence of the need to carefully regulate the NAS/melatonin ratio.This better integrates previously disparate data on GBM/GSC as well as providing clear future research and treatment options.
