Scientists at the University of Texas UT Southwestern Medical Center’s Institutional Research Institute in Texas (United States) have discovered a new metabolic vulnerability and a particularly aggressive type of pulmonary cancer cancer in recent years. with mutations in two key genes, KRAS and LKB1, which are prognostic and serious, and which, in addition, do not respond to immunotherapy.
“Solíamos thinks that the Mayor of tumors depends on the same set of metabolic pathways for growth, but in the last decade we have learned that this is an excessive simplification”, explains one of the researchers of the study, Ralph DeBerardinis. On the contrary, on the other hand, the different subclasses of tumors have particular metabolic needs that surge from mutations in key claws. “Understand the specific combinations of mutations that promote the growth of the tumor and the metastasis can allow the design of therapies in the midst of patients”, affirma, about the possible contribution of these hallucinations to precision medicine.
While it is believed that the mutations in the KRAS or in the LKB1 can alter the metabolism individually, they are known about the metabolic necessities when both genes are mutated in the same tumor. To discover new metabolic deficiencies, scientists compare the propensities of KL tumors genetically engineered with tumors that contain different mutations and normal pulmonary disease.
Thus, during the study, recently published in ‘Nature Metabolism’, scientists discovered that the biosynthesis life of hexosamine is active in KL tumors. These halozgos fueron consistent gracias to previous research in DeBerardinis laboratory, that show that the KL cells reprogram the metabolism of carbon and nitrogen. This manner, crecen, pero also increases its sensitivity to particular metabolic inhibitors.
THE PROCESS OF GLICOSILATION
The biosynthesis life of the hexosamine allows the cells to modify the proteins through a process called glycosylation, which facilitates the transport and secretion of proteins. Specifically, it is believed that the high protein production dose that feeds the KL tumor requires the activation of hexosamine biosynthesis via.
Thus, with the end of unfolding forms of inhibition in this way, investigators identify the enzyme GFPT2 as a responsible key in KL tumors. Thus, the genetic silencing or the chemical inhibition of this enzyme suppresses the growth of KL tumors in ratios, but only small effect in the growth of tumors that contain only the KRAS mutation. In addition, the hallucinations indicate the selective importation of hexosamine biosynthesis via KL tumors and suggest that GFPT2 may be a target for this aggressive subtype of pulmonary cancer in smallpox.
“Given that there is no specific inhibitor against GFPT2, our next step is to block certain steps in the path of glycosilation that may be therapeutically beneficial,” explained the postdoctoral fellowship conducting the DeBerard perspective study. “In the long run, there are options that can help keep the crime and the propagation of these aggressive tumors at bay,” he said.