In January 2024, professor Shen Baiyong's team at the Pancreas Center-Shanghai Key Laboratory of Translational Research in Pancreatic Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, published a research paper in Nature Medicine titled “Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma”. The team conducted a prospective observational study that included a total of 1 171 pancreatic cancer patients who underwent radical resection. First, paired samples of tumors from 191 pancreatic ductal adenocarcinoma (PDAC) patients were obtained by microdissection and subjected to proteomic analysis, which revealed unique protein modules of pancreatic tumors, particularly those related to chemotherapeutic drug sensitivity. Further, the research team established a prognostic risk model for pancreatic cancer at the proteomic level and validated the validity and reliability of this prognostic model with an external cohort. Using multicenter and large sample data, the study constructed and validated the generalizability of two protein markers in predicting the efficacy of chemotherapy in pancreatic tumors.
The incidence of cachexia in pancreatic cancer is high, which seriously affects the therapeutic effect and survival rate of patients. There is currently no effective intervention for tumor cachexia, so studying its regulatory mechanism has important clinical significance. In 2024, Professor Li Min's team from the Health Science Center of the University of Oklahoma published a research report on Cancer Cell entitled "The crosstalk between macroscopic and cancer cells potentials pancreatic cancer cachexia", which first revealed the relationship between the immune microenvironment (macrophages) of pancreatic cancer and the body's macro environment cachexia (muscle atrophy), opening up a new direction and new intervention ideas for the study of pancreatic cancer cachexia.
In 2024, Xue Jing's research team from Shanghai Jiao Tong University School of Medicine published a research paper in the journal Cancer Cell titled “Tumor Cell inflammatory dysregulation shapes cancer associated fibroblasts heterogeneity to metabolically support pancreatic cancer”. Studies have found that deletion of the tumor-intrinsic SET domain containing 2 (SETD2) releases bone morphogenetic protein 2 (BMP2) signals through abnormal increases in H3K27Ac, leading to the differentiation of cancer-associated fibroblasts (CAFs) cells toward a lipid-rich phenotype. Lipid-rich CAFs cells provide lipids to tumor cells through the ABCA8a transporter and enhance mitochondrial oxidative phosphorylation metabolism. Taken together, this study links epigenetic dysregulation of CAFs cells to tumor cells and highlights previously unrecognized metabolic crosstalk between CAFs cells and pancreatic tumor cells. In addition, the study also proposed using oxidative phosphorylation as a potential strategy for targeted treatment of patients with SETD2-deficient pancreatic ductal adenocarcinoma, providing new ideas for precise diagnosis and treatment.
Objective: This study aimed to investigate the correlation between the use of glucose-lowering drugs and the risk of pancreatic cancer through propensity score matching (PSM), which provides a scientific basis for clinical decision-making.
Methods: This study retrospectively analyzed the clinical data of patients diagnosed with type 2 diabetes mellitus (T2DM) and treated with glucose-lowering drugs in Nanjing Drum Tower Hospital between 2000 and 2023. The patients were divided into two groups: those with T2DM alone and those with T2DM combined with pancreatic cancer. PSM was employed to align the baseline characteristics of patients across groups, minimizing the impact of confounding factors. According to the use of glucose-lowering drugs, the correlation between the use of various types of glucose-lowering drugs and the occurrence of pancreatic cancer was explored by logistic regression analysis, and the drug influencing factors that might potentially affect the occurrence of pancreatic cancer were screened out. Additionally, the relationship between the use of glucose-lowering medications, both as monotherapy and in combination, and the occurrence of pancreatic cancer was further analyzed.
Results: The logistic regression analyses showed that previous use of sulfonylureas was significantly associated with pancreatic cancer in patients with T2DM, and previous use of dipeptidyl peptidase-4 (DPP-4) inhibitors was weakly associated with pancreatic cancer, and sulfonylureas [odds ratio (OR)=0.631，95% CI: 0.415-0.961，P=0.032] and dipeptidyl peptidase-4 (DPP-4) inhibitors (OR=0.639，95% CI: 0.388-1.052，P=0.078) may be associated with a reduced risk of pancreatic cancer in T2DM patients. Other drugs, including insulin, metformin, α-glucosidase inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, were not significantly associated with pancreatic cancer development. In a further analysis of glucose-lowering treatment regimens, it was shown that metformin in combination with other oral glucose-lowering agents was associated with pancreatic cancer [adjustment OR (aOR)=0.463， 95% CI：0.224-0.959， P=0.038] and may be a protective factor for pancreatic carcinogenesis.
Conclusion: The use of sulfonylureas and DPP-4 inhibitors in T2DM patients is related to the reduction of pancreatic cancer, and compared with the use of drugs alone, the use of drugs combined with oral hypoglycemic drugs can further reduce the incidence of pancreatic cancer.
Pancreatic cancer is a highly malignant digestive system tumor with poor prognosis. Its incidence is closely related to the level of regional development. Epidemiology shows that with the progress of urbanization, the proportion of obese people in the world is increasing over the years. Meanwhile, obesity has also been found to be one of the risk factors for pancreatic cancer. However, the mechanism of obesity regulating pancreatic cancer is still unclear at present. Researches show that obese people with pancreatic cancers have different tumor pathological mechanisms and higher risk of surgical complications. Therefore, this article will review the potential transformation mechanism between microscopic pathological changes and clinical manifestations of obesity related pancreatic cancer.
Pancreatic cancer has an insidious onset and a high degree of malignancy, and due to the limited efficacy of traditional treatments such as surgery and chemotherapy, this tumor has been one of the malignant tumors with the highest morbidity and mortality rates. In recent years, cell therapy, which utilizes and modifies the patient's own immune cells to target and kill tumor cells, is gradually becoming one of the potential alternatives to traditional treatment of tumors, and has achieved positive results in hematologic tumors. However, cell therapy in solid tumors, such as pancreatic cancer, is still in the research stage, and although it has achieved some efficacy, it is still full of challenges. In this review, the mechanism of chimeric antigen receptor-T cells (CAR-T), T cell receptor-T cells (TCR-T), and tumor infiltrating lymphocytes (TILs) in cell therapy and the efficacy in the treatment of pancreatic cancer were thoroughly discussed. Meanwhile, the main reasons for the poor effect of cell therapy in pancreatic cancer and the current research progress in improving the effect of cell therapy are preliminarily analyzed.
Pancreatic cancer is a malignant tumor with extremely poor prognosis, and its biological behavior is closely related to its genetic characteristics. Traditional preclinical research models struggle to accurately simulate the complex genetic heterogeneity and histological characteristics of pancreatic cancer. In recent years, the development of organoid models and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has provided new tools for pancreatic cancer research. Organoids can simulate the genetic and histological features of primary tumors, while CRISPR technology enables precise genetic manipulation in organoids. CRISPR Gene-Editing Organoids can model the occurrence and evolution of pancreatic cancer, conduct gene function analysis, and perform drug screening. This review discusses the recent advancements in the application of organoid models combined with CRISPR technology in pancreatic cancer research, which are expanding our understanding of pancreatic cancer.
Pancreatic fibrosis is an important pathological feature of pancreatic cancer and chronic pancreatitis, and plays an important role in the progression of pancreatic cancer and chronic pancreatitis. Pancreatic fibrosis blocks the chemotherapy drugs from reaching the cancer cells to do their job and also affects the stiffness of the pancreatic tissue. Therefore, it is important to assess the degree of pancreatic fibrosis as an adjunct to surgical and chemotherapeutic treatments for pancreatic cancer and chronic pancreatitis. In recent years, there have been new research advances and technological breakthroughs in non-invasive diagnostic methods for pancreatic fibrosis. The fields of CT, ultrasound elastography and magnetic resonance imaging have extended new imaging techniques, yielded new imaging indices to assess the degree of pancreatic fibrosis. In this paper, we have collected relevant literatures since 2018 to describe the research progress related to non-invasive diagnostic methods for pancreatic fibrosis.
