Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor with early systemic metastasis, poor prognosis, and extremely limited treatment options. Moreover, pancreatic cancer is resistant to most treatment methods, and the 5-year relative survival rate is less than 10%. Therefore, people urgently need to find new targets for the treatment of pancreatic cancer. Inspired by the significantly up-regulated expression of SDCBP in deep-sea fish to adapt to the hypoxia microenvironment in the deep sea, the team of Professor Hao Jihui, president of the Cancer Hospital of Tianjin Medical University, identified that the new target SDCBP would promote the progress of pancreatic cancer, and then screened out zinc pyrithione (ZnPT) from the drug bank approved by the US Food and Drug Administration (FDA). It was found that ZnPT could significantly inhibit the expression of SDCBP in pancreatic cancer. In the future, the treatment scheme targeting SDCBP may become a promising treatment strategy for pancreatic cancer. The relevant research papers were recently published in the international journal Gastroenterology. SDCBP is significantly related to the metastasis of pancreatic cancer. In the past 20 years, Hao Jihui's team has been exploring the hypoxia microenvironment of pancreatic cancer, revealing some of the key regulatory mechanisms, and found that the hypoxia environment will up regulate the hypoxia inducible factor HIF-1, thus activating the transcriptional expression of Fascin, LASP1, IGFBP2, LIMS1 and other key molecules in pancreatic cancer cells, thereby affecting pancreatic cancer cell apoptosis, invasion and metastasis Biological behaviors, such as anaerobic glycolysis and tumor angiogenesis, ultimately promote the progress of pancreatic cancer. During the study of interdisciplinary literature, the team found that in order to adapt to the deep-sea hypoxic microenvironment, the expression level of SDCBP in various organs of the deep-sea flounder was significantly upregulated. "This result provides us with profound inspiration and enables us to compare tumors and tumor hypoxic microenvironments with deep-sea fish and deep-sea hypoxic microenvironments." The first author of the paper, associate professor Liu Jing of the Cancer Hospital of Tianjin Medical University, introduced that tumor cells are also like fish living in deep-sea hypoxic microenvironments, upregulating the expression of relevant genes to maintain survival in order to proliferate, invade, and metastasize. The team identified that SDCBP was significantly related to the metastatic behavior of pancreatic cancer through single cell sequencing of multiple samples of pancreatic cancer in situ and metastatic lesions from the Pancreatic Cancer Center of Tianjin Medical University Cancer Hospital. The center's retrospective clinical cohort study showed that the median total survival and relapse free survival of pancreatic cancer patients in the high SDCBP group were significantly shorter than those in the low SDCBP group. In vitro and in vivo studies have shown that SDCBP can significantly promote the proliferation and metastasis of pancreatic cancer. In addition, organoid, PDX and other models proved that the treatment scheme targeting SDCBP can significantly inhibit the progress of pancreatic cancer and reduce tumor load. "In this study, we used organ like, xenotransplantation model of human tumor tissue, primary cell lines, etc. to highly simulate the growth environment of pancreatic cancer outside the human body, so as to carry out research in a state highly close to the real tumor microenvironment of the human body." Liu Jing said. Explore the mechanism of action of new targets Why does the expression of SDCBP affect pancreatic cancer? The team further explored the mechanism of SDCBP
Edit：Ying Ying Responsible editor：Shen Chen
Source：digitalpaper.stdaily.com
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