Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by poor prognosis, therapeutic resistance, and frequent recurrence. Current therapeutic options for PDAC include surgery, radiotherapy, immunological and targeted approaches. However, all these therapies provide only a slight improvement in patient survival. Consequently, the discovery of novel specific targets is becoming a priority to develop more effective treatments for PDAC. Mucin 1 (MUC1), a transmembrane glycoprotein, is aberrantly glycosylated and frequently overexpressed in pancreatic cancer. Recent studies highlighted the role of this oncoprotein in pancreatic carcinogenesis and its involvement in the acquisition of typical aggressive features of PDAC, like local invasion, metastases, and drug resistance. This review explores the mechanisms by which MUC1 contributes to cancer onset and progression, with a focus on its potential role as a biomarker and novel therapeutic target for pancreatic adenocarcinoma treatment.

Lateral Spreading Tumors (LSTs) are a type of non-polypoid lesion known for their flat morphology, which often leads to them going undetected. However, especially nongranular (NG) LSTs have the potential for malignant transformation. Recent advances in endoscopic technologies have improved the detection of these lesions. Despite growing research interest in their role in colorectal cancer (CRC) development, a comprehensive molecular characterization of LSTs is still lacking. The aim of this review is to highlight the current knowledge of the molecular characteristics of LSTs, that may help in determining whether LSTs can be prognostic indicators and identifying cases where they may rapidly progress to CRC through characteristic molecular pathways. From a mutational point of view, LSTs seem to be more closely associated with inflammatory bowel diseases (IBDs) than with polypoid lesions. Nonetheless, they have peculiar epigenetic and genetic traits, which set them apart from other adenomas or bowel diseases. Elucidating their role in CRC development would provide benefits for their classification and management, by enhancing clinical surveillance strategies for patients diagnosed with these lesions in order to improve the efficient prevention of colorectal cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor clinical outcomes and limited responsiveness to conventional treatments. Beyond delayed diagnosis, its high mortality is linked to limited treatment choices and resistance to chemotherapy. Neoplastic cells characterized by stem-like features and epithelial–mesenchymal transition (EMT) activation are crucial drivers of drug resistance and metastatic progression. Consequently, targeting these cellular programs could represent a promising therapeutic strategy for PDAC. N-acetyl-L-aspartic acid (NAA) is an endogenous metabolite, mainly localized in the central nervous system, where it facilitates acetate storage for lipid metabolism. Previous studies established its antineoplastic effect in neuroblastoma, promoting a more differentiated phenotype of cancer cells. Here we investigated the effects of NAA on BxPC-3 pancreatic cancer cells using both 2D and 3D models. NAA treatment induced a dose-dependent reduction in cell proliferation and led to a significant downregulation of stemness-associated surface markers, with concomitant upregulation of E-cadherin. Furthermore, NAA significantly enhanced cellular radiosensitization with a reduction in caveolin-1 and increased efficacy of gemcitabine in PDAC cells. Collectively, these results confirmed the anticancer activity of NAA and provide a rationale for further investigation of its synergistic effects with radiotherapy to yield better PDAC treatments.