Nat Metabol: Scientists hope to develop a new potential treatment for malignant non-small cell lung cancer

January 11, 2021 // -- In a recent study published in the international journal Nature Metabolism, scientists from the University of Texas Southwestern Medical Center and other institutions discovered a new metabolism in a highly invasive form of non-small cell lung cancer. Weakness ( metabolic vulnerability ) , the results of the study may help develop new therapies to treat cancer patients with mutations in the KRAS and LKB1 genes , which tend to have poor prognosis and are not usually responsive to immunotherapy .
. Ralph DeBerardinis, M.D., said: 'We used to think that most tumors relied on the same metabolic pathfours to grow, but over the past decade we've found that this may be an oversimplification.
instead, different tumor substates have specific metabolic needs due to mutations in key genes, and understanding how these specific combinations of mutations promote tumor growth and metastasis may help patients develop new, individualized anti-cancer therapies.
Photo Source: Elizabeth LieuKRAS or LKB1 mutations change the metabolism of cells alone, and researchers don't yet know exactly what the metabolic needs of cancer cells are when both genes mutate in the same tumor; to uncover new metabolic weaknesses in cells, scientists have genetically engineered KL tumors in mice with KL tumors that carry different mutations and cells in normal lungs. Metabolic properties were compared; the researchers found that HBP, hexosamine biosynthesis pathway is active in KL tumors, and the findings are consistent with previous scientists' findings that KL cells are able to reprogram the cell's carbon and nitrogen metabolism, which promote cell growth and increase its sensitivity to specific metabolic inhibitors.
HBP promotes cell modification of proteins through a process called glycosylation, which promotes protein transport and secretion, and the production of high-rate proteins that promote KL tumor growth is thought to require activation of HBP; Hereditary silence or chemical inhibition of this enzyme can inhibit the growth of KL tumors in mouse bodies, but does not seem to have any effect on the growth of tumors containing only KRAS mutations;
In conclusion, researcher Dr. Jiyeon Kim points out that since there are no specific inhibitors against GFPT2, our next step is to look at whether blocking specific steps in the glycosylation pathrain can yield therapeutic benefits;
() Original source: Kim, J., Lee, H.M., Cai, F. et al. The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer. Nat Metab 2, 1401–1412 (2020). doi：10.1038/s42255-020-00316-0