Christodoulou, Marianna

Pancreatic cancer comprises different subtypes, where most cases include ductal adenocarcinoma (PDAC). It is one of the deadliest tumor types, with a poor prognosis. In the majority of patients, the disease has already spread by the time of diagnosis, making full recovery unlikely and increasing mortality risk. Despite developments in its detection and management, including chemotherapy, radiotherapy, and targeted therapies as well as advances in immunotherapy, only in about 13% of PDAC patients does the overall survival exceed 5 years. This may be attributed, at least in part, to the highly desmoplastic tumor microenvironment (TME) that acts as a barrier limiting perfusion, drug delivery, and immune cell infiltration and contributes to the establishment of immunologically ‘cold’ conditions. Therefore, there is an urgent need to unravel the complexity of the TME that promotes PDAC progression and decipher the mechanisms of pancreatic tumors’ resistance to immunotherapy. In this review, we provide an overview of the major cellular and non-cellular components of PDAC TME, as well as their biological interplays. We also discuss the current state of PDAC therapeutic treatments and focus on ongoing and future immunotherapy efforts and multimodal treatments aiming at remodeling the TME to improve therapeutic efficacy.

Dietary exposure to acrylamide (AA) has been linked with carcinogenicity in the gastrointestinal (GI) tract. However, epidemiologic data on AA intake in relation to cancer risk are limited and contradictory, while the potential cancer-inducing molecular pathways following AA exposure remain elusive. In this study, we collected mechanistic information regarding the induction of carcinogenesis by dietary AA in the colon, using an established animal model. Male Balb/c mice received AA orally (0.1 mg/kg/day) daily for 4 weeks. RNA was extracted from colon tissue samples, followed by RNA sequencing. Comparative transcriptomic analysis between AA and mock-treated groups revealed a set of differentially expressed genes (DEGs) that were further processed using different databases through the STRING-DB portal, to reveal deregulated protein–protein interaction networks. We found that genes implicated in RNA metabolism, processing and formation of the ribosomal subunits and protein translation and metabolism are upregulated in AA-exposed colon tissue; these genes were also overexpressed in human colon adenocarcinoma samples and were negatively correlated with patient overall survival (OS), based on publicly available datasets. Further investigation of the potential role of these genes during the early stages of colon carcinogenesis may shed light into the underlying mechanisms induced by dietary AA exposure.