Glutamine metabolism has been established as an important metabolic pathway for pancreatic cancer, but its importance in colon cancer has previously been unclear.

New research from Osaka University has found that the metabolism of colorectal cancer, which is distinct from that of pancreatic cancer, is dependent on previously uncharacterised genomic alterations and not restricted to KRAS mutation alone. 

Colorectal cancer can survive under the condition of glucose depletion while retaining TCA cycle activity.

The cells’ survival relies on a delicate balance between energy and reactive oxygen species (ROS) production.

Glutamate dehydrogenase 1 (GLUD1) and SLC25A13 have pivotal roles under glucose-deprived conditions and are associated with tumour aggressiveness and colorectal cancer prognosis.

These proteins may serve as new targets in the treatment of refractory colorectal cancer.

"We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained TCA cycle activity and ATP production under such conditions. Furthermore, we identified the importance of GLUD1 and SLC25A13 in nutritional stress.", says Hideshi Ishii. "[These] may serve as new targets in treating refractory colorectal cancer, which survives in malnutritional microenvironments."

Source: Osaka University