Pancreatic cancer is a highly malignant digestive system tumor with a poor prognosis. Most pancreatic cancer patients are diagnosed at an advanced stage or even metastasis due to its highly aggressive characteristics and lack of typical early symptoms. Thus, an early diagnosis of pancreatic cancer is crucial for improving its prognosis. Currently, screening is often applied in high-risk individuals to achieve the early diagnosis of pancreatic cancer. Fully understanding the risk factors of pancreatic cancer and pathogenesis could help us identify the high-risk population and achieve early diagnosis and timely treatment of pancreatic cancer. Notably, accumulating studies have been undertaken to improve the detection rate of different imaging methods and the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) which is the golden standard for pancreatic cancer diagnosis. In addition, there are currently

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies with an extremely poor prognosis. Energy metabolism reprogramming, an emerging hallmark of cancer, has been implicated in the tumorigenesis and development of pancreatic cancer. In addition to well-elaborated enhanced glycolysis, investigating the role of reprogramming of amino acid metabolism has sparked great interests in recent years. The rewiring amino acid metabolism orchestrated by genetic alterations contributes to pancreatic cancer malignant characteristics including cell proliferation, invasion, metastasis, angiogenesis and redox balance. In the unique hypoperfused and nutrient-deficient tumor microenvironment (TME), the interactions between cancer cells and stromal components and salvaging processes including autophagy and macropinocytosis play critical roles in fulfilling the metabolic requirements and supporting growth of PDAC. In this review, we elucidate the recent advances in the amino acid metabolism reprogramming in pancreatic cancer and the mechanisms of amino acid metabolism regulating PDAC progression, which will provide opportunities to develop promising therapeutic strategies.

Digestive cancers are the leading cause of cancer-related death worldwide and have high risks of morbidity and mortality. Histone methylation, which is mediated mainly by lysine methyltransferases, lysine demethylases, and protein arginine methyltransferases, has emerged as an essential mechanism regulating pathological processes in digestive cancers. Under certain conditions, aberrant expression of these modifiers leads to abnormal histone methylation or demethylation in the corresponding cancer-related genes, which contributes to different processes and phenotypes, such as carcinogenesis, proliferation, metabolic reprogramming, epithelial-mesenchymal transition, invasion, and migration, during digestive cancer development. In this review, we focus on the association between histone methylation regulation and the development of digestive cancers, including gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, as well as on its clinical application prospects, aiming to provide a new perspective on the management of digestive cancers.

Background Pancreatic cancer’s poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear. Methods Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis Results We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis. Conclusions These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis.

Pancreatic cancer is one of the most serious health issues in developed and developing countries, with a 5-year overall survival rate currently <9%. Patients typically present with advanced disease due to vague symptoms or lack of screening for early cancer detection. Surgical resection represents the only chance for cure, but treatment options are limited for advanced diseases, such as distant metastatic or locally progressive tumors. Although adjuvant chemotherapy has improved long-term outcomes in advanced cancer patients, its response rate is low. So, exploring other new treatments is urgent. In recent years, increasing

The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic and environmental features in their pathogenesis, obesity amplifies the impact of genetic susceptibility and environmental factors on DM. The ectopic expansion of adipose tissue and excessive accumulation of certain nutrients and metabolites sabotage the metabolic balance via insulin resistance, dysfunctional autophagy, and microbiome-gut-brain axis, further exacerbating the dysregulation of immunometabolism through low-grade systemic inflammation, leading to an accelerated loss of functional β-cells and gradual elevation of blood glucose. Given these intricate connections, most available treatments of obesity and type 2 DM (T2DM) have a mutual effect on each other. For example, anti-obesity drugs can be anti-diabetic to some extent, and some anti-diabetic medicines, in contrast, have been shown to increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both obesity and T2DM. Besides guaranteeing the availability and accessibility of all the available diagnostic and therapeutic tools, more clinical and experimental investigations on the pathogenesis of these two diseases are warranted to improve the efficacy and safety of the available and newly developed treatments.

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