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The neoplastic epithelium of pancreatic cancer exists within a dense stroma that is recognized as a critical mediator of disease progression. This Review discusses our current understanding of the three principal constituents of pancreatic cancer stroma, their effect on the prevalent immune landscape and promising therapeutic targets within this compartment.
Irritable bowel syndrome is one of the most common gut disorders worldwide and is defined according to patterns of gastrointestinal symptoms that might be limited in their applicability to all countries and cultures. This Review provides an overview of the global burden of irritable bowel syndrome and discusses the implications for the care of patients worldwide.
Mammalian livers are characterized by an alteration of chromosome numbers, or polyploidy. In this Review, Desdouets and collaborators describe the regulation of polyploidy in liver development and pathophysiology, and discuss the mechanisms of hepatocyte polyploidization and its role in liver tumorigenesis.
The biological effects of cytokines in intestinal homeostasis and disease occur as a result of JAK–STAT signalling. This Review describes the current understanding of JAK–STAT signalling in intestinal homeostasis and inflammatory bowel disease as well as the rationale for therapeutically targeting this pathway.
Rectal cancer treatment has evolved towards a multidisciplinary approach to disease management. This Review examines the essential components of rectal cancer management through a multidisciplinary team, with a focus on the effect of this approach and the elements used for staging and developing the treatment plan.
The enteric nervous system (ENS) is essential for life and controls the function of the gastrointestinal tract. Here, an overview of sensory transduction and neural circuits in the ENS is provided, yielding insights into the generation of gastrointestinal motility.
The gut microbiota has been linked to non-alcoholic fatty liver disease (NAFLD), but metabolic confounding factors, such as obesity and diabetes, complicate analysis. This Review provides a broad insight into microbiome signatures for human NAFLD and explores issues with disentangling them from underlying metabolic disorders.
Exclusion diets are popular in the management of irritable bowel syndrome (IBS). This Review outlines the mechanisms by which food might lead to symptoms in IBS and discusses different approaches to how exclusion diets can be evaluated in randomized controlled trials.
Interactions between intestinal epithelial cells, the gut microbiota and immune cells have a key role in maintaining gut homeostasis. This Review describes how epithelial recognition of bacteria through Toll-like receptors participates in establishing homeostasis, and how dysregulation of these receptors can lead to dysbiosis, increasing susceptibility to colitis and tumorigenesis.
Organoid technology has emerged as a powerful method for studying gastrointestinal cancers. This Review describes organoid models of gastrointestinal cancers, such as colorectal and liver cancer, and discusses how they can be used in basic and translational research in fields such as drug discovery and personalized medicine.
The incidence of early-onset colorectal cancer (in patients <50 years old) is increasing at an alarming rate. This Review highlights potential risk factors and putative mechanisms that drive this disease, and suggests likely areas for fruitful research, including diet, stress and antibiotics.
Alterations in the gut microbiota and metabolite profiles of patients with IBD have been described. In this Review, Lavelle and Sokol discuss these alterations and their pathophysiological basis, and identify future targets for precision therapeutic modulation.
The small intestine is a key site for the absorption of nutrients, including lipids. In this Review, the physiology and biochemistry of intestinal fat absorption during health and disease is discussed, including insights into enterocyte biology and clinical disorders of intestinal fat absorption.
KRAS mutations are identified in >80% of patients with pancreatic ductal adenocarcinoma and tend to be associated with reduced overall survival. This Review discusses the role of oncogenic KRAS in the biology, diagnosis, prognosis and treatment of pancreatic cancer.
Radiotherapy is used to treat malignancies including gastrointestinal cancers but resistance to radiation can occur owing to biological alterations within the tumour and/or the surrounding microenvironment. Radiosensitizers are needed to improve treatment response to radiation. This Review discusses strategies being used to enhance radiosensitivity in gastrointestinal cancers according to the hallmarks of cancer.
Several big data ‘omics’ studies have analysed hepatocellular carcinoma (HCC). This Review describes omics studies in HCC and their potential in drug discovery and as candidate biomarkers. The application of emerging new artificial intelligence methods in HCC drug discovery is also discussed.
Epigenetic modifications and regulators, including DNA methylation, histone modifications and non-coding RNA species, have key pathophysiological roles in colorectal cancer (CRC). This Review outlines these epigenetic aberrations in CRC and their potential as diagnostic, prognostic and predictive biomarkers and therapeutic targets.
