Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.

Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area.

Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.