Primary glioma, as well as secondary metastases, provide significant treatment challenges. An understanding
of the biological underpinnings of glioma is likely to provide new pharmaceutical targets that will improve
patient survival. Here, we look at the role that the kynurenine pathways and associated tyrptophan catabolites
(TRYCATs) play in glioma, linking this to changes in oxidative and nitrosative stress (O&NS), immuneinflammatory
activity, the aryl hydrocarbon receptor (AhR), and the melatoninergic pathways. It is suggested that
the interactions of O&NS and the immune-inflammatory processes in glioma contribute to the induction of the
TRYCATs via the kynurenine activation of the AhR, leading to increased indoleamine 2,3-dioxygenase, which deprives
tryptophan for the necessary serotonin that is required as a precursor for the melatoninergic pathways. A diverse array of data pertaining
to glioma can be linked to these pathways, including changes in miRNAs, epigenetic processes, estrogen receptors, 14-3-3, chromosome
4q35, neurotrophins, tristetraprolin and the N-acetylserotonin (NAS)/melatonin ratio.
As many of these factors directly or indirectly act on the melatoninergic pathways, including variations in the NAS/melatonin ratio, it is
suggested that the melatoninergic pathways may act as a hub that co-ordinate the multitude of changes occurring in glioma. Consequently,
the melatoninergic pathways may be a significant pharmaceutical target for the treatment of this still very poorly managed condition.