Introduction:The microbiota is recognized for its impact on both human health and disease. The human microbiota is made up of trillions of cells, including bacteria, viruses, and fungi. The largest population of microbes reside in the gut, prompting research for better understanding of the impact of gastrointestinal microbiota in different diseases. Evidence from numerous studies has pointed out the role of commensal microbes as key determinants of cancer pathogenesis. Moreover, gut microbiota may play an important role in chemoresistance; consequently, this knowledge might be important for novel strategies to improve anticancer treatment efficacy. Areas covered: We describe the role of microbiota in different gastrointestinal cancer types (esophageal, gastric, colorectal, hepatocellular and pancreatic-biliary tract cancers). Moreover, we analyzed the impact of the microbiota on resistance to anticancer therapies, and, lastly, we focused on possibilities of microbiota modulation to enhance anticancer therapy efficacy. Expert opinion: Increasing evidence shows that gut microbiota might influence resistance to anticancer treatment, including conventional chemotherapy, immunotherapy, radiotherapy, and surgery. Therefore, a better knowledge of gut microbiota and its interactions with anticancer drugs will enable us to develop novel anticancer treatment strategies and subsequently improve the cancer patients' outcome.

The prognosis of metastatic pancreatic cancer remains poor despite the recent progress on modern chemotherapeutic regimens, such as FOLFIRINOX, gemcitabine and nab-paclitaxel. A better understanding of the altered signalling pathways and the importance of stroma and the immune environment in pancreatic cancer have led to the development of new clinical trials with promising results. In the present review, a general outline of current first-and second-line therapies is provided. Further, new therapeutic possibilities are reviewed, in particular EGFR and VEGF inhibitors, immunotherapy and PARP inhibitors.

Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-β). Besides its double-edged role as a tumor suppressor and activator, TGF-β causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation. Additionally, TGF-β induces inhibin and activin, causing weight loss and muscle depletion, while MIC-1/GDF15, a member of the TGF-β superfamily, leads to anorexia and so, indirectly, to muscle wasting, acting on the hypothalamus center. Against this background, the blockade of TGF-β is tested as a potential mechanism to revert cachexia, and antibodies against TGF-β reduced weight and muscle loss in murine models of pancreatic cancer. This article reviews the role of the TGF-β pathway and to a minor extent of other molecules including microRNA in cancer onset and progression with a special focus on their involvement in cachexia, to enlighten whether TGF-β and such other players could be potential targets for therapy.

Noncoding RNAs play important regulatory roles in diverse biological processes and their misregulation might lead to different diseases, including cancer. Previous studies have reported the evolving role of miRNAs as new potential biomarkers in cancer diagnosis, prognosis, as well as predictive biomarkers of chemotherapy response or therapeutic targets. In this review, we outline the involvement of noncoding RNA in pancreatic cancer, providing an overview of known miRNAs in its diagnosis, prognosis and chemoresistance. In addition, we discuss the influence of non-coding RNAs in the metastatic behavior of pancreatic cancer, as well as the role of diet in epigenetic regulation of non-coding RNAs in cancer, which can, in turn, lead the development of new prevention’s techniques or novel targets for cancer therapy.