Bile Acids and Microbiota Interplay in Pancreatic Cancer.

Evidence suggests the involvement of the microbiota, including oral, intra-tumoral and gut, in pancreatic cancer progression and response to therapy. The gut microbiota modulates the bile acid pool and is associated with maintaining host physiology. Studies have shown that the bile acid/gut microbiota axis is dysregulated in pancreatic cancer. Bile acid receptor expression and bile acid levels are dysregulated in pancreatic cancer as well. Studies have also shown that bile acids can cause pancreatic cell injury and facilitate cancer cell proliferation. The microbiota and its metabolites, including bile acids, are also altered in other conditions considered risk factors for pancreatic cancer development and can alter responses to chemotherapeutic treatments, thus affecting patient outcomes. Altogether, these findings suggest that the gut microbial and/or bile acid profiles could also serve as biomarkers for pancreatic cancer detection. This review will discuss the current knowledge on the interaction between gut microbiota interaction and bile acid metabolism in pancreatic cancer.

Can the molecules carried by extracellular vesicles help to diagnose pancreatic cancer early?

BACKGROUND: Pancreatic cancer is a deadly malignancy mainly because of its asymptomatic onset which prevents the implementation of the primary tumour's resection surgery, leading to metastatic spread resistant to chemotherapy. Early-detection of this cancer in its initial stage would represent a game changer in the fight against this disease. The few currently available biomarkers detectable in patients' body fluids lack sensitivity and specificity. SCOPE OF REVIEW: The recent discovery of extracellular vesicles and their role in promoting cancer's advancement has boosted interest in researching their cargo, to find reliable early detection biological markers. This review examines the most recent discoveries in the analysis of potential extra vesicle-carried biological markers for the early detection of pancreatic cancer. MAJOR CONCLUSIONS: Despite the advantages of using extracellular vesicles for early diagnosis, and the promising findings of extracellular vesicle-carried molecules possibly functional as biomarkers, until now there are no validated markers derived from extracellular vesicles available to be used in the clinic. GENERAL SIGNIFICANCE: Further studies in this direction are urgently required to provide what would be a major asset for defeating pancreatic cancer.

Modified lipidomic profile of cancer-associated small extracellular vesicles facilitates tumorigenic behaviours and contributes to disease progression.

Metabolic rewiring is a key feature of cancer cells, which involves the alteration of amino acids, glucose and lipids to support aggressive cancer phenotypes. Changes in lipid metabolism alter cancer growth characteristics, membrane integrity and signalling pathways. Small extracellular vesicles (sEVs) are membrane-bound vesicles secreted by cells into the extracellular environment, where they participate in cell-to-cell communication. Lipids are involved in the formation and cargo assortment of sEVs, resulting in their selective packaging in these vesicles. Further, sEVs participate in different aspects of cancer development, such as proliferation, migration and angiogenesis. Various lipidomic studies have indicated the enrichment of specific lipids in sEVs derived from tumour cells, which aid in their pathological functioning. This paper summarises how the modified lipid profile of sEVs contributes to carcinogenesis and disease progression.

Therapeutic potential of cannabinoids in combination cancer therapy.

Derivatives of the plant Cannabis sativa have been used for centuries for both medical and recreational purposes, as well as industrial. The first proof of its medicinal use comes from ancient China, although there is evidence of its earlier utilization in Europe and Asia. In the 19th century, European practitioners started to employ cannabis extracts to treat tetanus, convulsions, and mental diseases and, in 1851, cannabis made its appearance in the Pharmacopoeia of the United States as an analgesic, hypnotic and anticonvulsant. It was only in 1937 that the Marijuana Tax Act prohibited the use of this drug in the USA. The general term Cannabis is commonly used by the scientific and scholar community to indicate derivatives of the plant Cannabis sativa. The word cannabinoid is a term describing chemical compounds that are either derivate of Cannabis (phytocannabinoids) or artificial analogues (synthetic) or are produced endogenously by the body (endocannabinoids). A more casual term "marijuana" or "weed", a compound derived from dried Cannabis flower tops and leaves, has progressively superseded the term cannabis when referred to its recreational use. The 2018 World health organisation (WHO) data suggest that nearly 2.5% of the global population (147 million) uses marijuana and some countries, such as Canada and Uruguay, have already legalised it. Due to its controversial history, the medicinal use of cannabinoids has always been a centre of debate. The isolation and characterisation of Δ9 tetrahydrocannabinol (THC), the major psychoactive component of cannabis and the detection of two human cannabinoid receptor (CBRs) molecules renewed interest in the medical use of cannabinoids, boosting research and commercial heed in this sector. Some cannabinoid-based drugs have been approved as medications, mainly as antiemetic, antianorexic, anti-seizure remedies and in cancer and multiple sclerosis patients' palliative care. Nevertheless, due to the stigma commonly associated with these compounds, cannabinoids' potential in the treatment of conditions such as cancer is still largely unknown and therefore underestimated.