Search Results (668)

Pancreatic adenocarcinoma is one of the most aggressive malignancies, with a steadily increasing incidence rate. Due to the asymptomatic nature of early cancer and frequent late diagnosis, only 10–20% of patients are considered for radical treatment. In approximately 40% of patients, local advancement precludes primary surgical treatment, and in approximately half of patients, the cancer is diagnosed at the metastatic stage. Treatment of advanced pancreatic cancer is based on systemic therapy, while a growing number of studies are focusing on the potential use of molecularly targeted agents. The median survival time for metastatic patients treated with FOLFIRINOX chemotherapy is 11 months, compared to 8.5 months for patients treated with gemcitabine and nab-paclitaxel-based chemotherapy. Olaparib in the maintenance treatment of patients with advanced pancreatic cancer prolongs the time to progression compared to placebo but does not affect median overall survival. Immunotherapy and targeted therapy have so far been used in a narrow group of patients with a specific molecular profile, but further research on this cancer offers a real opportunity to develop new treatment approaches. This review article is based on the NCCN (National Comprehensive Cancer Network) guidelines and publications available in the PubMed database. Full article

Background: Pancreatic cancer is the least survivable malignancy, with five-year survival below 10%. Its vague, non-specific symptoms contribute to late diagnosis and poor outcomes. Targeted education for healthcare professionals, students, patients, carers, and the public may improve awareness, confidence, and early help-seeking. This scoping review aimed to map and synthesize peer-reviewed evidence on pancreatic cancer education, identifying intervention types, outcomes, and gaps in knowledge. Methods: A scoping review was undertaken using the Joanna Briggs Institute (JBI) framework and the Arksey and O’Malley framework and reported in accordance with PRISMA-ScR guidelines. The protocol was registered on the Open Science Framework. Four databases (MEDLINE, Embase, CINAHL, PsycINFO) were searched for English-language, peer-reviewed studies evaluating educational interventions on pancreatic cancer for healthcare students, professionals, patients, carers, or the public. Grey literature was excluded to maintain a consistent methodological standard. Data were charted and synthesised narratively. Results: Nine studies (2018–2024) met inclusion criteria, predominantly from high-income countries. Interventions targeted students and professionals (n = 3), patients (n = 2), the public (n = 2), or mixed groups (n = 2), using modalities such as team-based learning, workshops, virtual reality, serious games, and digital animations. Four interrelated themes were identified, encompassing (1) Self-efficacy; (2) Knowledge; (3) Behavior; and (4) Acceptability. Digital and interactive approaches demonstrated particularly strong engagement and learning gains. Conclusions: Pancreatic cancer education shows clear potential to enhance knowledge, confidence, and engagement across diverse audiences. Digital platforms offer scalable opportunities but require quality assurance and long-term evaluation to sustain impact. The evidence base remains limited and fragmented, highlighting the need for validated outcome measures, longitudinal research, and greater international representation to support the integration of education into a global pancreatic cancer control strategy. Future studies should also evaluate how educational interventions influence clinical practice and real-world help-seeking behaviour. Full article

Background/Objectives: Fibroblast activation protein (FAP), which is abundantly expressed in cancer-associated fibroblasts (CAFs) across various epithelial malignancies, has emerged as a promising target for molecular imaging and radionuclide therapy. Although several reviews have addressed FAP-targeted diagnostics, a comprehensive synthesis integrating molecular biology, diagnostic performance, and early therapeutic development remains limited. This review summarises the current evidence on radionuclide-labelled FAP inhibitors (FAPIs), with particular emphasis on their diagnostic utility, emerging therapeutic applications, and the structural features that shape their biological behaviour. Methods: A structured literature search was conducted across PubMed, Scopus, and Web of Science, focusing on FAPI-based imaging and therapy. Results: Diagnostic studies consistently demonstrate high tumour-to-background contrast for [⁶⁸Ga]Ga and [¹⁸F]-labelled FAPI radiotracers, particularly in tumours with prominent stromal components such as pancreatic, colorectal, breast, and head and neck cancers. FAPI PET/CT often surpasses [¹⁸F]FDG in lesion conspicuity in the brain, liver, and peritoneum. Therapeutic evidence shows encouraging tumour retention and safety profiles for agents such as [¹⁷⁷Lu]Lu-FAP-2286 and [⁹⁰Y]Y-FAPI-46, while α-emitting radiotracers (e.g., [²²⁵Ac]Ac-FAPI-04) demonstrate potent antitumor effects in preclinical models. Conclusions: Radiolabelled FAPI radiotracers hold significant potential as dual diagnostic and therapeutic agents, particularly for desmoplastic tumours with high CAF content. Nonetheless, clinical evidence remains in its early stages, and substantial questions persist regarding dosimetry, intertumoral variability in FAP expression, and optimal ligand selection for therapy. Continued development of next-generation FAPI constructs, along with well-designed prospective trials, will be crucial in defining the future role of FAPI-based theranostics in oncology. Full article

Neoantigen-based immunotherapies harness somatic mutations as tumor-specific targets and represent a major advance in personalized cancer treatment. Since neoantigens are presented exclusively on cancer cells, they enable highly selective T-cell recognition with minimal off-tumor toxicity. Neoantigen vaccines are rapidly emerging as a versatile class of personalized cancer immunotherapies designed to prime tumor-specific T cells by targeting somatic mutations unique to each patient’s tumor. Multiple types of neoantigen vaccines, using peptide, mRNA, and DNA, have shown feasibility, safety, and immunogenicity across diverse solid tumors. Emerging comparative data indicate that the vaccines using peptide-pulsed dendritic cells (DCs) elicit higher per-epitope CD8⁺ T cell responses than mRNA-based vaccines, likely due to more efficient class I presentation of synthetic peptides and ex vivo-loaded DCs. In contrast, mRNAs, despite their capacity of targeting multiple neoantigen peptides simultaneously, often induce CD4⁺-dominant responses due to immunodominance patterns during antigen processing. Recent clinical trials in melanoma, glioblastoma, pancreatic cancer, and other types of cancer have demonstrated not only robust immune activation but also encouraging relapse-free outcomes when administered in adjuvant settings. Treatment timing strongly influenced immune responsiveness; patients with early-stage disease or those vaccinated after surgical resection generally exhibit more preserved systemic immunity and greater vaccine-induced T cell expansion compared to those with advanced disease. Future progress will rely on improved neoantigen prediction, including incorporation of post-translationally modified antigenic targets and acceleration of manufacturing pipelines to ensure timely, personalized vaccine delivery. Collectively, neoantigen vaccines offer substantial promise for integration into next-generation cancer treatment strategies. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains a high-burden disease worldwide with increasing incidence, poor prognosis, and high mortality. Complete surgical resection is the only potentially curative treatment; however, due to a lack of symptoms in the early stages, most patients have advanced disease when diagnosed. Type 2 diabetes mellitus (T2DM) is a significant health concern characterized by hyperglycemia, insulin resistance, and impairment in insulin secretion. T2DM is linked with PDAC, sharing a complex bidirectional relationship. Therefore, dual causality between the two diseases represents significant challenges in practice, distinguishing existing T2DM as a PDAC risk factor from newly onset, potentially pancreatic cancer-related diabetes (PCRD). Evidence showed that new-onset diabetes (NOD) may serve as a biomarker for early diagnosis of PDAC, and several risk prediction models were developed to identify high-risk patients for further intervention. Although early PDAC detection is important, widespread screening is not currently recommended for T2DM patients due to a lack of cost-effective, efficient screening modalities. However, further risk stratification in diabetic patients is warranted to support a targeted screening strategy with economic viability. Diabetes confers ≈2-fold PDAC risk overall, with the highest relative risk in the first 2–3 years after diagnosis. Strategies using clinical signs (age ≥50–60 years, unintentional weight loss, rapid HbA1c escalation/insulin initiation) and predictive risk scores (e.g., ENDPAC) can triage NOD patients for magnetic resonance imaging/computed tomography (MRI/CT) and endoscopic ultrasound (EUS). A targeted screening approach may allow early diagnosis that could improve the prognosis of PDAC patients. This narrative review aims to synthesize current evidence linking T2DM and PDAC; delineate risk factors within diabetes populations; appraise predictive models and biomarkers for differentiating PCRD from typical T2DM; outline pragmatic, risk-adapted screening strategies, especially for NOD, and identify additional areas where further research is needed. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a high rate of recurrence and a dismal prognosis. Studies have shown that pancreatic cancer stem cells (PCSCs) are a subpopulation that contributes to tumor progression, resistance to therapeutics, and metastasis, making them a key subpopulation to target for treatment. Gedunin (GD), a natural compound derived from Azadirachta indica (neem), has shown anticancer properties in pancreatic cancer cells, but its effects on PCSCs remains unclear. This study evaluated the effects of GD in pancreatic cancer stem cells, highlighting its impacts on tumor growth and progression and focusing on its impact on the sonic hedgehog (Shh) signaling pathway. Methods: Functional assays were performed to assess the effect of GD on the sphere-forming ability, colony formation, and self-renewal of PCSCs. Athymic mice xenograft models were utilized to evaluate the tumor suppression effect of GD in vivo. Furthermore, the anticancer effect of GD on PCSCs was assessed using both in vitro and in vivo limiting dilution assay. GD-induced changes in Shh signaling and key stem cell marker expressions in PCSCs were evaluated. Results: GD effectively inhibited tumor growth in xenograft models and reduced the percentage of PCSCs. GD was effective in decreasing PCSCs’ proliferative, self-renewal, and colony-forming capacity. GD decreased the protein expression levels of key Shh signaling markers Gli1 and Shh, stem cell markers SOX2, Nanog, and Oct4, metastasis-related proteins MMP-2, MMP-3, and MMP-9, and EMT markers Tgf1, Slug, Snail, and Twist in both PDAC cells and PCSCs. We demonstrated a significant decrease in the spheroid formation and self-renewal capacity of the (ALDH+) PCSC population following GD treatment in HPAC cells, indicating its potential antagonistic effects on PCSCs. GD was highly effective in reducing tumor volume, stemness, and metastasis in both early and late chemotherapy. In vivo limiting dilution assay using CD133+/LGR5+ PCSC xenografts demonstrated that GD reduces tumor growth, metastasis, and stemness associated with PCSCs by downregulating the expression of Shh and Gli1. GD treatment also reduced micrometastatic lesions in the lung, liver, and brain, as identified using H&E staining. Conclusions: The findings highlight GD’s potential as a promising therapeutic candidate for PDAC, with the ability to target both bulk tumor cells and PCSCs. By simultaneously suppressing tumor growth, stemness, and metastatic spread, GD may contribute to more effective treatment strategies and improved patient outcomes. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, typically diagnosed at an advanced stage. The identification of prodromal symptoms could support earlier detection. Among these, depression is frequently reported, raising the question of whether it may represent not only a reactive response but also a paraneoplastic manifestation. Methods: We conducted a narrative review of clinical, epidemiological and biological literature published between 1988 and 2025. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science using predefined keywords related to pancreatic cancer, depression, prodromal symptoms, cytokines, and the kynurenine pathway. Eligible studies included clinical cohorts, population-based analyses, biological investigations, and case reports exploring the temporal or mechanistic link between depression and PDAC. Results: A substantial proportion of patients (10–20%) exhibit depressive symptoms in the months preceding the clinical diagnosis of pancreatic cancer. In several cases, depression occurs independent of weight loss and new-onset diabetes. Biological evidence highlights the involvement of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), NF-κB signaling, and activation of the tryptophan–kynurenine pathway (IDO), suggesting a link between tumor-related processes and mood alterations. These mechanistic findings are actually hypothesis-generating, deriving mainly from small clinical cohorts and preclinical models. Clinically, depression is associated with reduced adherence to treatment, poorer quality of life, and shorter survival. However, no specific depressive phenotype has been identified. Conclusions: Depression may represent a potential prodromal symptom of pancreatic cancer, reflecting systemic biological processes as well as psychological reactions. Its utility as a standalone marker remains limited; future studies should integrate psychiatric, clinical and biological biomarker assessments to enhance early clinical diagnosis. Full article

Gastrointestinal (GI) cancers represent a heterogeneous group of malignant neoplasms arising from the digestive tract, including gastric, colorectal, hepatic, pancreatic, and biliary cancers. These tumors represent a major public health challenge due to their aggressive nature and poor prognosis. Although significant progress has been made in diagnostic imaging, endoscopy, and multimodal therapies, early detection remains difficult. Conventional serum biomarkers often lack sufficient sensitivity and specificity for reliable diagnosis, prompting a growing interest in identifying novel, minimally invasive biomarkers. In this context, liquid biopsy is emerging as a revolutionary tool in oncology. Among its components, extracellular vesicles (EVs) have gained increasing attention because they carry a wide range of molecular cargoes that reflect the biological state of their tumor of origin. In particular, EV-associated microRNAs (miRNAs) hold great promise as biomarkers for early cancer detection, real-time monitoring of disease progression, and assessment of therapeutic response. This review discusses the diagnostic and prognostic potential of EVs as novel biomarkers in GI cancers, emphasizing EV-contained miRNAs as a key resource for the development of personalized and precision medicine strategies. Full article

Single-cell sequencing (scRNA-seq) has emerged as a pivotal technology for deciphering the complex cellular heterogeneity and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), positioning it as a critical tool for informing novel therapeutic strategies. This review explores how scRNA-seq reveals diverse cellular subpopulations and their functional roles within the PDAC TME, including malignant epithelial cells with transitional phenotypes, heterogeneous cancer-associated fibroblasts (CAFs), functionally distinct immune cells such as tumor-associated neutrophils (TANs) and macrophages (TAMs), and actively participating neural components like Schwann cells. These cellular constituents form specialized functional units that drive tumor progression, immune evasion, neural invasion, and therapy resistance through metabolic reprogramming, immunosuppressive signaling, and cellular plasticity. The review further examines technological advances in single-cell sequencing from 2023 to 2025, focusing on sample preprocessing innovations, multi-omics integration (combining transcriptomics with epigenomics and proteomics), spatial resolution enhancements, and customized computational tools that address PDAC-specific challenges. Clinically, single-cell sequencing enables precise cellular subtyping, identification of novel biomarkers, and development of personalized therapeutic approaches, including combination therapies targeting specific cellular subpopulations and their interactions. Despite these advances, significant challenges remain in standardizing clinical applications such as liquid biopsy for early detection and tumor microenvironment assessment for diagnostic staging, validating biomarkers like CLIC4, GAS2L1, Cytokeratins, Vimentin and N-cadherin in circulating tumor cells, and comprehensively integrating multi-omics data. Future research focusing on both technology refinement and biological validation will be essential for translating single-cell insights into improved diagnostic and therapeutic outcomes for pancreatic cancer. Full article

Background and Objectives: Cancer incidence patterns in South Korea have shifted markedly over the past two decades, with notable increases among younger generations. Despite growing concern regarding early-onset cancer, comprehensive assessments of long-term age-, period-, and cohort-specific trends across multiple cancer types remain limited. This study examined nationwide cancer incidence trends from 2001 to 2020 using Joinpoint regression and age–period–cohort (APC) modeling. Materials and Methods: A population-based analysis was conducted using Korea Central Cancer Registry (KCCR) data, including all primary malignant tumors diagnosed from 2001 to 2020. Incidence rates were calculated by sex and 5-year age groups and standardized to the mid-2000 Korean population. Joinpoint regression estimated annual percent change (APC) and average annual percent change (AAPC), accounting for overdispersion and autocorrelation. Independent temporal effects were evaluated through APC modeling using overlapping 10-year birth cohorts, with the 1961 cohort as the reference. Results: Incidence increased for prostate, kidney, breast, and pancreatic cancers, while stomach, liver, lung, and biliary cancers showed continued declines. Colon cancer rose until 2011 and decreased thereafter. More recent birth cohorts exhibited higher risks for prostate, kidney, and pancreatic cancers, whereas older cohorts showed elevated risks for stomach, liver, colon, and biliary cancers. Lung cancer trends diverged by sex, decreasing among men but increasing among women. Conclusions: Marked heterogeneity in long-term incidence patterns across cancer types and generations was identified. Rising rates of lifestyle- and obesity-associated cancers in more recent cohorts highlight the need for continued surveillance and targeted prevention strategies. APC-based evaluation provides essential insight into Korea’s evolving cancer landscape and supports future public health planning. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to late-stage diagnosis and limited therapeutic efficacy. The carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker in the management of PDAC. While CA19-9 has significant limitations as a screening or diagnostic tool, including low sensitivity for early-stage disease and a lack of expression in the Lewis antigen-negative population, its value in the post-diagnostic setting is well established. This review examines the production and clearance dynamics of CA19-9. It critically evaluates how these factors impact its role as a biomarker for prognosis, assessment of resectability, and real-time monitoring of therapeutic response and recurrence in patients with PDAC. We explore how the relatively short half-life and correlation with tumor burden make CA19-9 a dynamic tool for tracking disease progression and treatment efficacy, often providing insights that precede radiographic changes. This review concludes that, despite its limitations, CA19-9 remains an important, cost-effective, and widely accessible biomarker for the longitudinal management of patients with established pancreatic cancer. Its dynamic changes allow continuous real-time disease monitoring providing critical information for clinical decision-making. Full article

For decades, cancer risk has been explained mainly by local factors. However, emerging evidence shows that the oral microbiome acts as a systemic modifier of oncogenesis well beyond the head and neck. This review synthesizes clinical and mechanistic data linking dysbiotic oral communities, especially Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, to malignancies across gastrointestinal, respiratory, hepatobiliary, pancreatic, breast, and urogenital systems. We summarize organ-specific associations from saliva, tissue, and stool studies, noting the recurrent enrichment of oral taxa in tumor and peri-tumoral niches of oral, esophageal, gastric, colorectal, lung, pancreatic, liver, bladder, cervical, and breast cancers. Convergent mechanisms include the following: (i) persistent inflammation (lypopolysacharide, gingipains, cytolysins, and collagenases); (ii) direct genotoxicity (acetaldehyde, nitrosation, and CDT); (iii) immune evasion/suppression (TLR/NLR signaling, MDSC recruitment, TAN/TAM polarization, and TIGIT/CEACAM1 checkpoints); and (iv) epigenetic/signaling rewiring (NF-κB, MAPK/ERK, PI3K/AKT, JAK/STAT, WNT/β-catenin, Notch, COX-2, and CpG hypermethylation). Plausible dissemination along an oral–gut–systemic axis, hematogenous, lymphatic, microaspiration, and direct mucosal transfer enables distal effects. While causality is not yet definitive, cumulative data support oral dysbiosis as a clinically relevant cofactor, motivating biomarker-based risk stratification, saliva/stool assays for early detection, and microbiome-targeted interventions (periodontal care, antimicrobials, probiotics, and microbiota modulation) alongside conventional cancer control. Full article

Diabetic atherosclerosis results from the interplay between metabolic dysfunction and immune dysregulation and remains the major cause of mortality in patients with diabetes mellitus (DM) worldwide. Emerging evidence indicates that impaired immune checkpoint signaling, particularly through the PD-1/PD-L1 and CTLA-4 pathways, contributes to the chronic vascular inflammation characteristic of diabetic cardiovascular disease. These checkpoints normally help maintain vascular homeostasis by limiting proatherogenic immune responses. In type 2 diabetes (T2D), which accounts for 90–95% of cases, chronic hyperglycemia downregulates checkpoint expression in both immune effector cells and the vascular endothelium. In type 1 diabetes (T1D), autoimmune-mediated checkpoint failure within the pancreatic islets extends to the vascular tissues, creating an early cardiovascular risk through overlapping but distinct mechanisms. The loss of checkpoint regulation amplifies Th1 and Th17 responses while impairing regulatory T cell function and accelerating plaque formation and destabilization. Observations from cancer patients receiving checkpoint inhibitors, who exhibit increased cardiovascular events, further highlight the importance of these pathways in vascular integrity. Restoring checkpoint signaling through targeted interventions, combined with biomarker-driven stratification and personalized immune profiling, may provide new strategies for preventing or slowing atherosclerotic progression in patients with diabetes. Full article

Purpose: Root cause analysis carried out to establish the likely causes for pancreatic cancer not being diagnosed on previous imaging. Methods: Records of pancreatic cancer patients between 2016 and 2021 at two NHS providers were examined. Post-Imaging Pancreatic Cancer (PIPC) was defined as pancreatic cancer diagnosed 3–18 months after an index scan that did not report cancer. Index and diagnostic imaging were reviewed by two radiologists independently. An algorithm was developed to categorise PIPC. Results: 46 of 600 patients (7.7%) were classified as having PIPC, with 43 CT and 3 MRI scans undertaken 3–18 months before cancer diagnosis. The median age was 75.9 (IQR 69.6–80.2) years, with 58.7% female. PIPCs were categorised as focal lesion reported on index scan in the same pancreatic segment as diagnostic scan (2.2%); imaging changes associated with pancreatic cancer reported on index scan (17.4%); missed focal lesion or imaging changes associated with pancreatic cancer on index scan (26.1%); no focal lesion or imaging changes associated with pancreatic cancer on index scan (54.3%). Following exclusion of two patients (one declined investigations and one was too unwell), 16 of 46 (35%) PIPC patients could have been diagnosed earlier. Twelve had a missed focal lesion, and four had duct dilatation or a focal lesion reported but were inadequately investigated. Conclusions: Approximately three out of 100 pancreatic cancer patients could have been diagnosed earlier due to a missed lesion or inadequately investigated lesion or duct dilatation on index imaging. There are opportunities for earlier diagnosis of pancreatic cancer on imaging. Full article

Gastrointestinal cancers, including gastric, gastroesophageal junction, pancreatic, and biliary tract cancers, remain associated with poor outcomes due to late diagnosis and limited effective treatment options. Claudin-18.2 (CLDN18.2), a tight junction protein primarily found in the gastric epithelium and ectopically expressed in gastrointestinal tumors, has emerged as a promising therapeutic target across these diseases. This narrative review expands on existing discussions surrounding CLDN18.2-directed therapy in gastric and gastroesophageal cancer and provides a comprehensive, updated analysis of the rapidly evolving therapeutic landscape across multiple gastrointestinal malignancies, including pancreatic and biliary tract cancers. We summarize key developments following the approval of the monoclonal antibody zolbetuximab and critically evaluate emerging modalities, including bispecific antibodies, antibody–drug conjugates, and chimeric antigen receptor T-cell therapies, highlighting differences in mechanisms of action, efficacy, toxicity profiles, and mitigation strategies. We also discuss the clinical relevance of CLDN18.2 and PD-L1 co-expression, the rationale for pairing CLDN18.2-targeted therapy with immune checkpoint inhibitors, and early data supporting combination approaches. Additionally, we examine tumor heterogeneity, biomarker challenges, and emerging resistance mechanisms, alongside strategies to overcome them. Finally, we identify current limitations in the field, including inconsistent CLDN18.2 testing criteria, and outline prioritized future directions to optimize integration of CLDN18.2-directed therapies across gastrointestinal cancers. By looking beyond zolbetuximab and incorporating cross-platform comparison, immuno-oncology considerations, and multi-tumor context, this review provides a broad and forward-looking framework to guide clinical application and next-generation research in CLDN18.2-targeted therapy. Full article