On the 13th, the reporter learned from the People's Hospital of Wuhan University that the research team of Song Qibin, Yao Yi and Zhang Pingfeng from the Cancer Center of the hospital had made new breakthroughs in the research of lung cancer etiology and chemoradiotherapy response. Relevant research results were published in the latest issue of Nature Chemical biology. This research achievement reveals a new mechanism by which abnormal glucose metabolism promotes nucleotide synthesis, tumor growth, and radiochemotherapy resistance in tumor cells. It provides a new theoretical basis and further research direction for solving the problems of lung cancer occurrence, development, and treatment resistance. Metabolic reprogramming is the main feature of malignant tumors, including lung cancer, and has always been a focus and hotspot in the field of cancer research. Metabolic reprogramming can promote the synthesis of a large number of Metabolic intermediate to meet their rapid growth and proliferation needs. These intermediates include nucleotides, the basic building blocks of DNA and RNA as the basis of life materials. Nucleotides are also involved in a series of important biological events such as cell signal transduction. Previous studies have shown that the nucleotide De novo synthesis synthesis pathway in most tumor cells is generally abnormally activated, leading to Malignant transformation and therapeutic resistance of tumors. However, the key molecular mechanism has not been clarified, which is an important core scientific issue in this field. Focusing on this problem, the scientific research team of the People's Hospital of Wuhan University and the team of Professor Pei Huadong of Georgetown University in the United States found that the O-GlcNAc modification caused by abnormal glucose metabolism in lung cancer cells increased, which played a key role in De novo synthesis nucleotides synthesis, lung cancer occurrence and chemoradiotherapy resistance. This study also found that the abnormal activity of glucose metabolism in lung cancer cells would lead to the up regulation of O-GlcNAc modification and significant increase of the rate limiting enzyme Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) in the nucleotide De novo synthesis synthesis pathway. O-GlcNAc glycosyltransferase mediated modification of PRPS1 O-GlcNAc not only promotes the transformation of PRPS1 from monomer to hexamer, but also relieves the feedback inhibition effect of nucleotide products on PRPS1 itself, enhances the catalytic enzyme activity of PRPS1 through different mechanisms, thus further leading to abnormal increase of nucleotide De novo synthesis synthesis, malignant proliferation, and chemoradiotherapy resistance of lung cancer cells. (Outlook New Era Network)