Glutamine is an essential amino acid for the proliferation and viability of cancer cells, making it a critical target for cancer therapy.
With this understanding in mind, important microenvironment-dependent
effects of glutamine metabolism on tumor progression necessarily have implications for cancer patients considering exogenous glutamine supplementation.
Notably, the differential response between orthotopic and subcutaneous tumors suggests that tissue microenvironment significantly influences glutamine metabolism and utilization.
Hence, the absence of significant growth stimulation by supplementary glutamine in brain tumors might reflect the tight regulation of glutamine levels in the glutamine/glutamate cycle, in relation the blood-brain barrier.
Conversely, the significant growth stimulation observed in subcutaneous tumors via supplementary glutamine, suggests that systemically located malignancies outside the brain directly benefit from increased glutamine availability.
Furthermore, decreased intratumoral glutamine concentrations despite elevated serum levels, may indicate rapid glutamine consumption, supporting the glutamine addiction phenomenon described in many aggressive cancers.
As such, these insights can offer instruction as to the caution given to supplementary exogenous glutamine for cancer patients, depending on tissue of origin, and correspondingly, the potential requirement to employ pan-glutamic inhibitors such as 6-Diazo-5-Oxo-L-Norleucine as a primary intervention, pursuant to addressing the fundamental energy metabolism of disease.
