Editor’s recommendation: Pancreatic cancer, the “king of cancer”, has a strong insidious onset and a high mortality rate. The five-year survival period is less than 5%. The latest WHO forecast data shows that, In 2030, the death rate of pancreatic cancer will rise to the second place in global cancer deaths.
Pancreatic cancer, the “King of Cancer”, has a strong insidious onset, a high mortality rate, and a five-year survival rate of less than 5%. The latest WHO forecast data shows that, In 2030, the death rate of pancreatic cancer will rise to the second place in global cancer deaths. At present, the diagnosis and treatment of pancreatic cancer is facing four severe challenges: lack of effective biomarkers for early warning diagnosis; unknown molecular mechanism of hidden onset; lack of decisive drug targets; due to platinum drug resistance and frequent side effects, clinical treatment is difficult. There is a lack of safe and effective medicines. The reason is that the pathogenesis of pancreatic cancer is complex, and there is a lack of in-depth molecular scientific understanding and new research strategies.
Based on the preliminary research of pancreatic cancer metabolic profile and biomarkers, Shanghai Jiao Tong University Lv Haitao’s research group from the Institute of Systems Biomedicine/Key Laboratory of Systems Biomedicine Ministry of Education recently published an article titled “Functional metabolisms revealed the dual-activation of cAMP-AMP axis is a novel therapeutic target” in the international authoritative pharmacological journal “Pharmacological Research” of pancreatic cancer” research paper, focusing on the use of the newly developed functional omics Spatial Temporal Operative Real Metabolomics (STORM) strategy of the research group, a new precise identification, spatial visualization, dynamic capture and targeted regulation of cAMP-AMP axis is the key to pancreatic cancer It is determined that gemcitabine, a commonly used clinical drug, promotes the significant accumulation of AMP and cAMP by regulating the biosynthesis of ATP, the key substrate of AMP and cAMP, and then activates the phosphorylation process of AMPK signaling pathway and PKA signaling pathway, and the system exerts Inhibition of pancreatic cancer tumor growth.
There are three innovations in this study: building a new STORM functional metabolomics strategy to achieve precise characterization, spatial visualization, dynamic capture and targeted synthesis of pancreatic cancer-determining functional metabolites regulation; using the STORM strategy to discover a potential new target cAMP-AMP axis for the treatment of pancreatic cancer; this study will provide a new target for the rapid screening and evaluation of pancreatic cancer drug molecules. In addition, enhancing the targeting of gemcitabine to new targets through preparation optimization and other means will help improve its effectiveness in the treatment of pancreatic cancer.
The first author of the paper is Shanghai Jiao Tong University Institute of Systems Biomedicine/Systems Biomedical Education Liu Jingjing, a 2020 doctoral student in the key laboratory of the Ministry of Education, and Wang Tianyu, a 2019 master student (graduated), participated in part of the work. The corresponding author of the paper is Lu Haitao, a researcher at the Institute of Systems Biomedicine of Shanghai Jiaotong University/Key Laboratory of Systems Biomedicine of the Ministry of Education. The research work of this thesis has been supported by the Ministry of Science and Technology’s National Key R&D Program Project, National Natural Science Foundation of China, Shanghai Natural Science Foundation, National Center for Translational Medicine (Shanghai) Key Project, Agilent Technologies ACT-UR Award Project and Shanghai Academician Expert Workstation (Experts) Level) project and other support.
Paper link: https://doi.org/10.1016/j.phrs.2022.106554
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