Pancreatic cancer is a highly aggressive gastrointestinal tumor with limited treatment options, such as surgery and chemotherapy. Thus, further research into its pathogenesis and new treatments is necessary.

Fluorescence-activated cell sorting was employed to sort pancreatic cancer stem cells (PCSCs). Sphere formation assays and Cell Counting Kit-8 (CCK-8) assays were conducted to assess stemness and proliferation capacity. Quantitative real-time PCR and Western blot analysis were employed to assess gene expression levels. Furthermore, immunofluorescence microscopy and chromatin immunoprecipitation assays were conducted to examine alterations in signaling pathways and gene expression.

Quercetin and gemcitabine may inhibit PANC-1 cells and PCSCs by affecting energy metabolism. Chromatin immunoprecipitation assays revealed an interaction between STAT3 and CPT1B in PCSCs. Quercetin and gemcitabine might affect energy metabolism by inhibiting STAT3 and CPT1B. Manipulating STAT3 expression (overexpression plasmids and siRNA knockdown) altered CPT1B mRNA and protein expression. Although acetyl-CoA reversed the quercetin- and gemcitabine-induced expression of N-cadherin, DECR1, and ALDH, it had minimal influence on CPT1B and STAT3 levels.

Quercetin inhibits the expression of CPT1B via the STAT3 signaling pathway, affecting lipid metabolism and exerting antitumor effects. Furthermore, the combined administration of quercetin and gemcitabine exhibits enhanced therapeutic efficacy.

Calcium electroporation, an innovative technique, uses high-voltage pulses to introduce calcium ions into cells, leading to cell death and tumor growth inhibition. This review explores the potential of calcium electroporation as a promising therapeutic approach in cancer treatment. We provide an in-depth analysis of the underlying mechanisms by which calcium ions function within cells and how their introduction through electroporation can effectively induce cell death in cancer cells. Furthermore, we present a comprehensive overview of the current literature, covering both preclinical and clinical studies, to highlight the safety and efficacy of calcium electroporation in various cancer types, including melanoma, head and neck cancer, and breast cancer. We also discuss the distinct advantages of calcium electroporation over traditional cancer therapies, such as its specific targeting of cancer cells while sparing healthy cells. However, we also address the challenges and limitations associated with this technique, underscoring the need for further research. By providing a comprehensive examination of calcium electroporation, this review aims to contribute to understanding this emerging field and encourage further investigation into its potential as a novel cancer treatment strategy.

This study evaluates the effects of different high-intensity focused ultrasound irradiation (HIFU) methods on local tumor suppression and systemic antitumor effects, including the abscopal effect, in a mouse model of pancreatic cancer. To ascertain the efficacy of the treatment, pancreatic cancer cells were injected into the thighs of mice and HIFU was applied on one side using continuous waves or trigger pulse waves. Then, tumor volume, tissue changes, and immune marker levels were analyzed. Both the irradiation methods suppressed tumor growth, with the trigger pulse wave showing stronger effects and the difference being significant. Tumor suppression was also observed on the non-irradiated side, suggesting an abscopal effect. These effects vary depending on the irradiation method used. We conclude that HIFU induces both local tumor suppression and a systemic immune response, suggesting its potential for combination with immunotherapy for the treatment of pancreatic cancer.

Pancreatic cancer is one of the main causes of cancer-related deaths, especially pancreatic ductal adenocarcinoma, and it's characterized by a poor prognosis. The KRAS gene mutation is prevalent in about 85% of pancreatic cancer cases, which is a significant factor in the pathogenesis and development of pancreatic cancer, impacting cellular tumor growth, survival, and metastasis. The targeted disruption of mutant KRAS variants through the application of various CRISPR systems has led to a marked reduction in cell viability and proliferation in vitro, accompanied by significant inhibition of tumor growth in vivo.

This systematic study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search of PubMed, Google Scholar, and PLOS One for original research articles published up to June 2024. Studies included those involving CRISPR-Cas9 gene editing targeting KRAS mutations in human or animal models of pancreatic cancer. Data collection and quality assessment were performed independently by two reviewers.

The review identified numerous studies demonstrating the efficacy of CRISPR-Cas9 in targeting KRAS mutations. Results showed significant reductions in KRAS transcript levels, decreased tumor progression, and improved survival rates in experimental models. However, challenges such as off-target effects and efficient delivery methods were noted.

CRISPR-Cas9 gene editing shows significant promise as a therapeutic strategy for targeting KRAS mutations in pancreatic cancer. While the technology has demonstrated potential in preclinical studies, further research is needed to address challenges related to specificity, delivery, and long-term effects to facilitate its clinical application.

The KRAS G12D mutation is the most prevalent type of pancreatic cancer and is found in about 35% of patients. Numerous natural chemicals are frequently investigated in cancer treatment to decrease side effects. Resveratrol (RVT) is a polyphenol that can promote cancer cell apoptosis and improve chemotherapy efficacy in cancers. To enhance delivery rate and efficacy, the size of about 30 nm gold nanoparticles (GNPs) was synthesized and conjugated to resveratrol via polyvinylpyrrolidone (GRs) for high bioavailability. Compared to RVT and GNPs, GRs had less inflammatory response and less toxicity on RAW 264.7 cells. This suggests that the toxicity of resveratrol can be alleviated by conjugation with gold nanoparticles. The viability of the human pancreatic cancer cell line (AsPC-1) decreased in sequence of GRs > RVT > GNPs, suggesting an enhanced anticancer effect of the GRs compared to resveratrol (RVT) alone. In addition, the extent of apoptosis was much bigger with GRs compared to RVT and GNPs. The apoptotic effects were confirmed with cell cycle arrest and expression of apoptosis-related genes and proteins. Thus, GRs had a better extent of anticancer effect than RVT, suggesting that GRs be considered as one of the prospective anti-cancer drugs for pancreatic cancer treatment.

Ultra-high dose rate (>40 Gy/s, FLASH) radiation therapy (RT) provides equivalent tumor control while reducing normal tissue toxicity relative to conventional dose rate (CONV) RT. However, the mechanisms underlying the observed FLASH effect are unknown. We hypothesized that the preservation of mitochondrial integrity in nontumorigenic cells by FLASH RT could be a key factor in reducing normal tissue toxicity and improving overall treatment outcomes.

We examined mitochondrial health and function after CONV and FLASH in vitro, ex vivo, and in vivo through assays of metabolic flux, mitochondrial membrane potential, mitochondrial reactive oxygen species (ROS), mitochondrial DNA damage and copy number, mitochondrial morphology, and tumor growth and survival.

In in vitro assays, murine pancreatic cancer (PDAC) cells showed evidence of equal mitochondrial damage in response to CONV and FLASH, but nontumorigenic pancreatic cells were spared by FLASH. These results were recapitulated ex vivo, and mice treated with FLASH showed higher response rates and longer survival time than mice treated with CONV in an in vivo tumor model.

Collectively, these results suggest that FLASH spares mitochondrial function in nontumorigenic cells, but not in PDAC cells, relative to CONV. The preservation of mitochondrial integrity in nontumorigenic cells may be a key mechanism underlying the reduced normal tissue toxicity observed with FLASH RT.

Pancreatic cancer is one of the most lethal malignancies worldwide. It is characterized by poor prognosis, high mortality, and recurrence rates. Various modifiable and non-modifiable risk factors are associated with pancreatic cancer incidence. Available treatments for pancreatic cancer include surgery, chemotherapy, radiotherapy, photodynamic therapy, supportive care, targeted therapy, and immunotherapy. However, the survival rates for PC are very low. Regrettably, despite efforts to enhance prognosis, the survival rate of pancreatic cancer remains relatively low. Therefore, it is essential to investigate new approaches to improve pancreatic cancer treatment. By synthesizing current knowledge and identifying existing gaps, this article provides a comprehensive overview of risk factors, pathology, conventional treatments, targeted therapies, and recent advancements in nanocarriers for its treatment, along with various clinical trials and patents that justify the safety and efficacy of innovative carriers for drug delivery systems. Ultimately, this review underscores the potential of these innovative formulations to improve outcomes and contribute significantly to the advancement of Pancreatic Cancer treatment. Together, these insights highlight nano-formulations as a promising frontier for effectively treating Pancreatic Cancer.

Chemodynamic therapy (CDT) is a therapeutic method that uses a Fenton/Fenton-like reaction to convert intracellular H2O2 into highly cytotoxic ˙OH to effectively kill cancer cells. This method is adapted to the specific characteristics of the tumor microenvironment, boasting high selectivity and strong specificity among other advantages. However, CDT still faces challenges. Glutathione (GSH), which is present in high levels in the tumor microenvironment, can consume a large amount of ˙OH, significantly limiting the effectiveness of CDT. In this study, we synthesized a core-shell nanozyme (mSiO2@MnO2) with a composite structure comprising a mesoporous silica core and a manganese dioxide (MnO2) shell. The mesoporous structure was loaded with the chemotherapeutic drug genistein (Gen) and surface-modified with polyethylene glycol (PEG) to enhance its effectiveness in treating pancreatic cancer. This formulation, denoted as the Gen@mSiO2@MnO2-PEG nanocomplex enzyme, exhibits a dual action mechanism. Firstly, upon reaching tumor cells, it releases genistein for kinetic therapy and degrades the MnO2 shell. Secondly, GSH consumption triggers Fenton-like reactions to generate ˙OH, thereby enhancing CDT. At the cellular level, the Gen@mSiO2@MnO2-PEG nanocomplex enzyme demonstrates excellent biocompatibility. It induces the production of reactive oxygen species in the pancreatic cancer cell line PANC-1, disrupting the redox balance within tumor cells, and ultimately killing them. In vivo, the Gen@mSiO2@MnO2-PEG nanocomplex enzyme selectively accumulates at the tumor sites in PANC-1 tumor-bearing mice, resulting in the inhibition of tumor growth and metastasis. This study demonstrates that core-shell nanozymes serve as an effective platform for cancer therapy, enhancing the efficacy of combined chemotherapy and CDT for pancreatic cancer.

Multimodal temporal therapy orchestrated to leverage immunotherapy, tumor-targeted chemotherapy, and natural killer (NK) cell therapy may provide an opportunity to induce immunogenic cell death for tumor response and increased survival in patients with recurrent cancer. The interleukin-15 (IL-15) superagonist N-803, an enhancer of NK cells, CD4 + T cells, cytotoxic CD8 + T cells, and memory T-cell activity, combined with off-the-shelf PD-L1-targeted high-affinity NK (PD-L1 t-haNK) cells represent novel immunotherapies designed to overcome an immunosuppressive tumor microenvironment (TME). The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC). Here, we report the compassionate use treatment of this combination in a patient with recurrent, metastatic pancreatic cancer (mPC) after 3 lines of therapy. Under the initial single-patient Investigational New Drug (spIND) protocol, the patient received N-803, PD-L1 t-haNK cells, and the albumin doxorubicin conjugate aldoxorubicin for ~27 months. The patient's disease became stable on this regimen, and a transient complete response was observed by ~14 months of therapy. Due to progression, a second spIND protocol was designed whereby the patient received E-EDV-D682 plus EDV-GC for more than 24 months, which resulted in stable disease and the patient's continued survival at the time this report was written. The patient's extended survival despite the dire prognosis associated with recurrent mPC points to the merits of this temporal combination regimen in overcoming immuno-chemo resistance with enhanced immune activity required for tumor response and extended survival.

Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most formidable cancers, largely due to its distinct microenvironment characterized predominantly by extensive desmoplastic stroma. In this study, we synthesized three novel water-soluble fullerene-based nanomaterials targeting EGFR protein.

The direct amination of fullerene carbon atoms, was followed by conjugation with a modified derivative of the EGFR inhibitor-erlotinib, resulting in the formation of novel water-soluble fullerene derivatives.

Further investigation into PAN02 and AsPC-1 cell lines revealed that these fullerene nanomaterials could induce cell cycle arrest in the G0/G1 phase, corroborated by alterations in the expression levels of the p27 and cyclin E1 proteins. Additionally, mechanisms of cell death were identified as autophagy for C60BUT and C70BUT-ERL, and apoptosis for Gd@C82EDA-ERL nanomaterials.

Crucially, the study uncovered the efficacy of synthesized aminofullerenes in inhibiting the EGFR signaling pathway. The further toxicological studies of Gd@C82EDA-ERL fullerene on Drosophila melanogaster, underscored its potential for theranostic applications.

Cancer-associated fibroblasts (CAFs) are key components of tumor microenvironment and have been identified to be involved in modulating drug resistance in cancers by secreting molecules. Pancreatic cancer (PC) is a leading cause of cancer mortality with high aggressiveness. Gemcitabine (GEM) is one of primary antineoplastic drugs for PC. Collagen XVII (COL17A1) expression was found to be upregulated in GEM-resistant CAFs. Here, this study focused on investigating whether CAFs affected GEM resistance in PC by secreting COL17A1 and its associated mechanisms.

In total, 60 newly diagnosed PC patients only with GEM-based chemotherapy were recruited. Normal fibroblasts (NFs) and CAFs were isolated using fresh normal and resistant PC tissues. Human pancreatic duct epithelial (HPDE) cells were used for functional analyses. Levels of COL17A1 and Actinin Alpha 4 (ACTN4) were measured by using qRT-PCR and western blotting. Functional analyses were conducted using MTT, 5-ethynyl-2'-deoxyuridine, transwell, and sphere formation assays, respectively. The interaction between COL17A1 and ACTN4 was analyzed by Co-immunoprecipitation and immunofluorescence assays. Animal models were established for in vivo analysis.

CAF incubation promoted GEM resistance and enhanced the proliferation, invasion and stemness in GEM-resistant PC cells. COL17A1 was highly expressed in resistant CAFs and GEM-resistant PC cells, and CAF incubation could increase COL17A1 expression in resistant PC cells. Moreover, COL17A1 silencing in GEM-resistant PC cells or the incubation of COL17A1-decreased CAF with GEM-resistant PC cells could suppress GEM resistance and cell oncogenic phenotype progression. Mechanistically, COL17A1 interacted with ACTN4 protein, and the anticancer effects mediated by COL17A1-decreased CAFs in resistant PC cells were reversed by ACTN4 overexpression. In vivo assay also showed that COL17A1-decreased CAFs suppressed the growth and GEM resistance in PC by ACTN4.

CAFs-derived COL17A1 promoted GEM resistance and tumorigenesis in PC by interacting with ACTN4, suggesting a new method for overcoming GEM resistance in PC.

Pancreatic cancer is an aggressive tumor, which is often associated with a poor clinical prognosis and resistance to conventional chemotherapy. Therefore, there is a need to identify new therapeutic markers for pancreatic cancer. Although KIN17 is a highly expressed DNA‑ and RNA‑binding protein in a number of types of human cancer, its role in pancreatic cancer development, especially in relation to progression, is currently unknown. The present study verified the upregulation of KIN17 in pancreatic cancer using The Cancer Genome Atlas and Gene Expression Omnibus databases (GSE15471, GSE71989 and GSE62165), and identified an association between the PI3K/Akt/mTOR pathway and patient prognosis using publicly available datasets (Gene Expression Profiling Interactive Analysis). Immunohistochemistry was performed to determine the association between KIN17 and the pathological features of clinical pancreatic cancer samples. Furthermore, knockdown of KIN17 was shown to inhibit the migration and invasion of pancreatic cancer cells, and to reverse epithelial‑mesenchymal transition in pancreatic cancer cells through downregulation of Vimentin and N‑cadherin, and upregulation of E‑cadherin. Through various cellular experiments, the role of KIIN17 was explored in PI3K/AKT/mTOR activity. KIN17 inhibition was shown to suppress the migration and invasion of pancreatic cancer cells through PI3K/AKT/mTOR‑mediated autophagy. Furthermore, combined with mTOR inhibition, dual inhibition could enhance autophagy, leading to anti‑migratory and anti‑invasion effects in pancreatic cancer. In conclusion, the present study indicated that KIN17 may have a role in carcinogenesis and could serve as a prognostic biomarker of pancreatic cancer, owing to its high expression. In addition, KIN17 may be considered a potential therapeutic target with its knockdown having an inhibitory effect on pancreatic cancer.

Limited research has compared external beam radiotherapy (RT) to non-RT in patients with nonsurgical locally advanced pancreatic cancer (LAPC). Therefore, this study investigates the impact of RT on overall survival (OS) in patients with nonsurgical LAPC in a real-world context.

The authors conducted an analysis of patients with nonsurgical LAPC using data from the Surveillance, Epidemiology, and End Results (SEER) database. This analysis involved the utilization of Kaplan-Meier survival curves and multivariable Cox regression analyses.

A total of 5413 individuals with nonsurgical LAPC were included in this analysis. Among them, 2320 (42.9%) received RT, while 3093 (57.1%) underwent non-RT treatment. The median OS was 12.0 months for the RT group and 9.0 months for the non-RT group, with a statistically significant difference ( P <0.001). Multivariate analysis revealed that RT had a statistically significant impact on OS (HR, 0.86; 95% CI: 0.81-0.91; P <0.001). Propensity score matching analysis confirmed a statistically significant association of RT with improved OS (HR, 0.84, 95% CI: 0.79-0.90; P <0.001). These results remained consistent after conducting sensitivity analyses, subgroup analyses, and propensity score matching.

The study findings suggest that RT could be advantageous for patients with nonsurgical LAPC. Further investigations are warranted to explore the relationship between RT and OS.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events. In particular, we identified myoferlin (MYOF), a member of the ferlin family involved in membrane processes, as a functional splicing target of hnRNPLL. hnRNPLL depletion stimulates MYOF exon 17 retention to reduce the short isoform of MYOF (MYOFb) and inhibit metastasis. In contrast, hnRNPLL or MYOFb overexpression promoted pancreatic cancer cell migration and invasion. These results suggest that hnRNPLL is a critical factor for early PDAC metastasis. hnRNPLL and MYOFb may be potential therapeutic targets for PDAC.

Pancreaticoduodenectomy (PD) for patients with pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of postoperative complications (PoCs) and risk prediction of these is therefore critical for optimal treatment planning. We hypothesize that novel deep learning network approaches through transfer learning may be superior to legacy approaches for PoC risk prediction in the PDAC surgical setting.

Data from the US National Surgical Quality Improvement Program (NSQIP) 2002-2018 were used, with a total of 5,881,881 million patients, including 31,728 PD patients. Modelling approaches comprised of a model trained on a general surgery patient cohort and then tested on a PD specific cohort (general model), a transfer learning model trained on the general surgery patients with subsequent transfer and retraining on a PD-specific patient cohort (transfer learning model), a model trained and tested exclusively on the PD-specific patient cohort (direct model), and a benchmark random forest model trained on the PD patient cohort (RF model). The models were subsequently compared against the American College of Surgeons (ACS) surgical risk calculator (SRC) in terms of predicting mortality and morbidity risk.

Both the general model and transfer learning model outperformed the RF model in 14 and 16 out of 19 prediction tasks, respectively. Additionally, both models outperformed the direct model on 17 out of the 19 tasks. The transfer learning model also outperformed the general model on 11 out of the 19 prediction tasks. The transfer learning model outperformed the ACS-SRC regarding mortality and all the models outperformed the ACS-SRC regarding the morbidity prediction with the general model achieving the highest Receiver Operator Area Under the Curve (ROC-AUC) of 0.668 compared to the 0.524 of the ACS SRC.

DNNs deployed using a transfer learning approach may be of value for PoC risk prediction in the PD setting.

Gastric duplication cysts (GDCs) are rare congenital anomalies, often identified during infancy or childhood. Although typically benign, there have been sporadic reports of malignant transformations, including adenocarcinoma and rare mixed tumors. Herein, we describe a rare case of mixed pancreatobiliary ductal adenocarcinoma and squamous cell carcinoma occurring within a GDC in a 54-year-old Korean woman with a history of melena and hematemesis. Initial gastroscopy and positron emission tomography-computed tomography (PET-CT) revealed a protruding stomach mass. A laparoscopic total gastrectomy was performed, and histological examination confirmed a mixed carcinoma originating from an ectopic pancreas within the duplication cyst. This case is unique as it is the first reported instance in the world of mixed pancreatobiliary ductal adenocarcinoma and squamous cell carcinoma arising from an ectopic pancreas within a GDC. This highlights the importance of considering pancreatobiliary-type adenocarcinoma in the differential diagnosis of malignancies originating from GDCs, which has implications for treatment strategies.

Mutations of KRAS, CDKN2A, TP53, and SMAD4 are the four major driver genes for pancreatic ductal adenocarcinoma (PDAC), of which mutations of KRAS and TP53 are the most frequently recognized. However, molecular-targeted therapies for mutations of KRAS and TP53 have not yet been developed. To identify novel molecular targets, we newly established organoids with the Kras mutation (KrasmuOR) and Trp53 loss of function using Cre transduction and CRISPR/Cas9 (Krasmu/p53muOR) from murine epithelia of the pancreatic duct in KrasLSL-G12D mice, and then analyzed the proteomic and metabolomic profiles in both organoids by mass spectrometry. Hyperfunction of the glycolysis pathway was recognized in Krasmu/p53muOR compared with KrasmuOR. Loss of function of triosephosphate isomerase (TPI1), which is involved in glycolysis, induced a reduction of cell proliferation in human PDAC cell lines with the TP53 mutation, but not in PDAC or in human fibroblasts without TP53 mutation. The TP53 mutation is clinically recognized in 70% of patients with PDAC. In the present study, protein expression of TPI1 and nuclear accumulation of p53 were recognized in the same patients with PDAC. TPI1 is a potential candidate therapeutic target for PDAC with the TP53 mutation.

Pancreatic adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer deaths by 2030 and this is mostly due to therapy failure. Limited treatment options and resistance to standard-of-care (SoC) therapies makes PDAC one of the cancer types with poorest prognosis and survival rates [1,2]. Pancreatic tumors are renowned for their poor response to therapeutic interventions including targeted therapies, chemotherapy and radiotherapy. Herein, we review hallmarks of therapy resistance in PDAC and current strategies aiming to tackle escape mechanisms and to re-sensitize cancer cells to therapy. We will further provide insights on recent advances in the field of drug discovery, nanomedicine, and disease models that are setting the ground for future research.

Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to diagnose and treat effectively. Although there have been improvements in the 5-year overall survival rate, it is still very low at 12.5%. The limited efficacy of current therapies, even when PDAC is detected early, underscores the aggressive nature of the disease and the urgent need for more effective treatments. Clinical management of PDAC still relies heavily on a limited repertoire of therapeutic interventions, highlighting a significant gap between research efforts and available treatments. Over 4300 clinical trials have been or are currently investigating different treatment modalities and diagnostic strategies for PDAC, including targeted therapies, immunotherapies, and precision medicine approaches. These trials aim to develop more effective treatments and improve early detection methods through advanced imaging techniques and blood-based biomarkers. This review seeks to categorize and analyze PDAC-related clinical trials across various dimensions to understand why so few chemotherapeutic options are available to patients despite the numerous trials being conducted. This review aims to provide a comprehensive and nuanced understanding of the landscape of PDAC-related clinical trials, with the overarching goal of identifying opportunities to accelerate progress in drug development and improve patient outcomes in the fight against this devastating disease.

Surgical resection is the standard recommended treatment in localized pancreatic cancer. The benefit of neoadjuvant chemotherapy is still debated. The aim of this population-based study was to describe the pancreatic cancer surgical management.

An observational real-world study from the French Network of Cancer Registries sampled 638 pancreatic adenocarcinomas diagnosed in 2019. Characteristics of patients, tumours and recommended and administered treatments were collected. Operability of the patients and resectability of the tumours were described. A multivariate logistic regression was used to identify factors associated with the probability of having surgical resection.

Among the 263 (41 %) patients with M0 pancreatic adenocarcinomas, 202 patients (77 %) were considered operable and 157 (60 %) also had a tumour considered resectable. Upfront resection was recommended for 68 % and resection after neoadjuvant chemotherapy for 32 % of these patients. Among operable patients with resectable tumour, 36 % underwent upfront R0 resection, and 15 % achieved R0 resection following neoadjuvant chemotherapy. Eventually, among M0 pancreatic adenocarcinomas, age over 80 years (OR≥80 years vs < 65 years: 0.16 [0.06-0.39], p < 0.001) and WHO performance status over 0 (OR1-2 vs 0: 0.43 [0.24-0.79], p = 0.013) decreased the odds of having resection. R0 surgical resection was achieved in 61 % of patients selected for upfront surgical recommendation, and 29 % of those selected for a prior neoadjuvant chemotherapy.

In a non-selected population, one-third of patients with localized pancreatic cancer had a complete R0 surgical resection. Neoadjuvant chemotherapy did not achieve a resection rate similar to that of patients selected for upfront surgical indication.

Exploring more efficient pancreatic cancer drug screening platforms is of significant importance for accelerating the drug development process. In this study, we developed a high-sensitivity bioluminescence system based on smartphones and smart tablets, and constructed a pancreatic cancer drug screening platform (PCDSP) by combining the pancreatic cancer cell sensing model (PCCSM) on the multiwell plates (MTP). A smart tablet was used as the light source and a smartphone as the colorimetric sensing device. The smartphone dynamically controls the color and brightness displayed on the smart tablet to achieve lower LOD and wider detection ranges. We constructed PCCSM for 24 h, 48 h, and 72 h , and performed colorimetric experiments using both PCDSP and a commercial plate reader (CPR). The results showed that the PCDSP had a lower LOD than that of CPR. Moreover, PCDSP even exhibited a lower LOD for 24 h PCCSM testing compared to CPR for 48 h PCCSM testing, effectively shortening the drug evaluation process. Additionally, the PCDSP offers higher portability and efficiency compared with CPR, making it a promising platform for efficient pancreatic cancer drug screening.

The unresectable pancreatic head tumors develop obstructive jaundice and cholestasis during follow-up. Cholestasis is associated with complications and treatment options are endoscopic stenting (ES) and biliary bypass surgery (BBS).

The aim of the current study was to compare the safety and efficacy of biliary bypass surgery (BBS) and endoscopic stenting (ES) for cholestasis in advanced pancreas cancer.

This is a retrospective cohort of patients with cholestasis and unresectable or metastatic pancreas cancer, treated with BBS or ES. Short and long-term outcomes were evaluated. We considered the need for hospital readmission due to biliary complications as treatment failure.

A total of 93 patients (BBS=43; ES=50) were included in the study. BBS was associated with a higher demand for postoperative intensive care (37 vs.10%; p=0.002, p<0.050), longer intensive care unit stay (1.44 standard deviation±2.47 vs. 0.66±2.24 days; p=0.004, p<0.050), and longer length of hospital stay (7.95±2.99 vs. 4.29±5.50 days; p<0.001, p<0.050). BBS had a higher risk for procedure-related complications (23 vs. 8%; p=0.049, p<0.050). There was no difference in overall survival between BBS and ES (p=0.089, p>0.050). ES was independently associated with a higher risk for treatment failure than BBS on multivariate analysis (hazard ratio 3.97; p=0.009, p<0.050).

BBS is associated with longer efficacy than ES for treating cholestasis in advanced pancreatic cancer. However, the BBS is associated with prolonged intensive care unit and hospital stays and higher demand for intensive care.

Pancreatic cancer (PC) is a highly malignant solid tumor whose resistance to gemcitabine (GEM) chemotherapy is a major cause of poor patient prognosis. Although PC is known to thrive on malnutrition, the mechanism underlying its chemotherapy resistance remains unclear. The current study analyzed clinical tissue sample databases using bioinformatics tools and observed significantly upregulated expression of the deubiquitinase STAMBP in PC tissues. Functional experiments revealed that STAMBP knockdown remarkably increases GEM sensitivity in PC cells. Multiple omics analyses suggested that STAMBP enhances aerobic glycolysis and suppresses mitochondrial respiration to increase GEM resistance in PC both in vitro and in vivo. STAMBP knockdown decreased PDK1 levels, an essential regulator of the aerobic glycolytic process, in several cancers. Mechanistically, STAMBP promoted the PDK1-mediated Warburg effect and chemotherapy resistance by modulating E2F1 via direct binding to E2F1 and suppressing its degradation and ubiquitination. High-throughput compound library screening using three-dimensional protein structure analysis and drug screening identified the FDA drug entrectinib as a potent GEM sensitizer and STAMBP inhibitor, augmenting the antitumor effect of GEM in a patient-derived xenograft (PDX) model. Overall, we established a novel mechanism, via the STAMBP-E2F1-PDK1 axis, by which PC cells become chemoresistant in a nutrient-poor tumor microenvironment.

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.

Carnitine palmitoyltransferase 1C (CPT1C) is an enzyme that regulates tumor cell proliferation and metabolism by modulating mitochondrial function and lipid metabolism. Hypoxia, commonly observed in solid tumors, promotes the proliferation and progression of pancreatic cancer by regulating the metabolic reprogramming of tumor cells. So far, the metabolic regulation of hypoxic tumor cells by CPT1C and the upstream mechanisms of CPT1C remain poorly understood. Yin Yang 1 (YY1) is a crucial oncogene for pancreatic tumorigenesis and acts as a transcription factor that is involved in multiple metabolic processes. This study aimed to elucidate the relationship between YY1 and CPT1C under hypoxic conditions and explore their roles in hypoxia-induced proliferation and metabolic alterations of tumor cells. The results showed enhancements in the proliferation and metabolism of PANC-1 cells under hypoxia, as evidenced by increased cell growth, cellular ATP levels, up-regulation of mitochondrial membrane potential, and decreased lipid content. Interestingly, knockdown of YY1 or CPT1C inhibited hypoxia-induced rapid cell proliferation and vigorous cell metabolism. Importantly, for the first time, we reported that YY1 directly activated the transcription of CPT1C and clarified that CPT1C was a novel target gene of YY1. Moreover, the YY1 and CPT1C were found to synergistically regulate the proliferation and metabolism of hypoxic cells through transfection with YY1 siRNA to CRISPR/Cas9-CPT1C knockout PANC-1 cells. Taken together, these results indicated that the YY1-CPT1C axis could be a new target for the intervention of pancreatic cancer proliferation and metabolism.

As a key pathological feature of pancreatic ductal adenocarcinoma(PDAC), the dense extracellular matrix(ECM) limits the penetration of chemotherapy drugs and is involved in the formation of immunosuppressive microenvironment. Meanwhile, clinical practice has shown that the treatment strategy for ECM should consider its restriction of tumor cell metastasis, and the need for in-depth chemotherapy without destroying ECM is proposed. STAT3 inhibitors have been reported to regulate tumor microenvironment including interrupt the form of ECM. Therefore, we designed and established a micelle system MP@HA with in vivo targeting and responsive drug release function co-loading gemcitabine monophosphate and STAT3 inhibitor silibinin. The hyaluronic acid on the surface of the micelle can bind specifically to the CD44 molecule on the surface of tumor cells and help micelles accumulate at the tumor site. The nitroimidazole used to modify the polymeric skeleton can make the micellar structure collapse in response to hypoxia reduction conditions in the tumor environment, and release silibinin to widely regulate STAT3 molecules in the PDAC microenvironment. The polymer fragment attached with gemcitabine monophosphate can penetrate deep into PDAC tumors due to its small size and positive charge exposed, achieving deep chemotherapy. This research indicates a promising micelle system meeting complicated demands proposed in PDAC treatment to improve antitumor efficacy.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Malignant gastric outlet obstruction (mGOO) is a major condition affecting patients with periampullary tumors, including pancreatic cancer. The current treatment options include surgical gastroenterostomy, endoscopic stenting and more recently EUS-guided gastroenterostomy. Most studies comparing the outcomes of the three procedures focus on technical success, clinical success and safety. Several "occult" outcomes relevant to the patient's viewpoints and perspective may ultimately impact on cancer-related and overall survival, such as body mass composition, nutritional biomarkers, chemotherapy tolerance and patient-reported quality of life. The aim of this review is to provide an overview of potential key outcomes that should be explored in future comparative research around mGOO treatment options.

Small interfering RNA (siRNA) has been proved to be able to effectively down-regulate gene expression through the RNAi mechanism. Thus, siRNA-based drugs have become one of the hottest research directions due to their high efficiency and specificity. However, challenges such as instability, off-target effects and immune activation hinder their clinical application. This review explores the mechanisms of siRNA and the challenges in siRNA-based tumor therapy. It highlights the use of various nanomaterials - including lipid nanoparticles, polymeric nanoparticles and inorganic nanoparticles - as carriers for siRNA delivery in different therapeutic modalities. The application strategies of siRNA-based nanomedicine in chemotherapy, phototherapy and immunotherapy are discussed in detail, along with recent clinical advancements. Aiming to provide insights for future research and therapeutic approaches.

Objective: The study aimed to explore the role of the Wnt/β-catenin signaling pathway in pancreatic cancer progression and chemoresistance, with a focus on identifying specific factors that distinguish between normal and tumor cells, thereby offering potential therapeutic targets.

Materials and Methods: We analyzed levels of total and phosphorylated eukaryotic translation initiation factor 4E (eIF4E) and β-catenin in pancreatic cancer and normal pancreatic tissues. Functional assays were used to assess the impact of eIF4E phosphorylation on β-catenin signaling, cell proliferation, and chemoresistance, with MNK kinase involvement determined through gene depletion studies. The MNK kinase inhibitor eFT508 was evaluated for its effects on eIF4E phosphorylation, β-catenin activation, and cell viability in both in vitro and in vivo models of pancreatic cancer.

Results: Both total and phosphorylated eIF4E, along with β-catenin, were significantly elevated in pancreatic cancer tissues compared to normal tissues. Phosphorylation of eIF4E at serine 209 was shown to activate β-catenin signaling, enhance cell proliferation, and contribute to chemoresistance in pancreatic cancer. Importantly, these effects were dependent on MNK kinase activity. Depletion of eIF4E reduced cell viability in both pancreatic cancer and normal cells, while depletion of MNK selectively decreased viability in pancreatic cancer cells. Treatment with eFT508 effectively inhibited eIF4E phosphorylation, suppressed β-catenin activation, and reduced pancreatic cancer cell growth and survival in vitro and in vivo, with minimal impact on normal cells.

Conclusions: The MNK-eIF4E-β-catenin axis plays a critical role in pancreatic cancer progression and chemoresistance, distinguishing pancreatic cancer cells from normal cells. Targeting MNK kinases with inhibitors like eFT508 presents a promising therapeutic strategy for pancreatic cancer, with potential for selective efficacy and reduced toxicity.

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death and presents the lowest 5-year survival rate of any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy, which remains the only curative treatment. Chemotherapeutic and gene therapy treatments are associated with adverse effects and lack specificity/efficacy. In this study, we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2) and mouse interleukin (mIL)-2 in human pancreatic BxPc-3 cells using immunocompromised and CD-3+ T-cell-reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in a regression in BxPc-3 xenograft volume compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in a significant difference from control at p < 0.05. Histological analysis of immunocompromised mice treated with TPV/∆66R/mCCL2 or TPV/∆66R/mIL-2 demonstrated multiple biomarkers indicative of increased severity of chronic, active inflammation compared to controls. In conclusion, TPV recombinants expressing mCCL2 and mIL-2 demonstrated a therapeutic effect via regression in BxPc-3 tumor xenografts. Considering the enhanced oncolytic potency of TPV recombinants demonstrated against PDAC in this study, further investigation as an alternative or combination treatment option for human PDAC may be warranted.

Despite recent improvements in oncology, diagnosis, and therapy, pancreatic cancer remains extremely difficult to cure due to its aggressive growth pattern with early invasion and distant metastases, chemoresistance, and a lack of effective screening modalities for early detection. Here, novel therapeutic approaches for treating pancreatic cancer are urgently needed. Recently, stem cells have drawn a lot of interest as a possible treatment for pancreatic cancer due to their ability to locate tumors. Though research over the last few decades has revealed some very exciting and promising new treatment approaches, the clinical success of these stem-cell based anti-cancer medicines has been quite limited. The most effective stem cell-mediated therapeutic options will only be available with a deeper understanding of the intricate molecular biology underlying pancreatic cancer and the subsequent identification of cancer stem cells as a novel target that promotes the growth of the cancer and resistance to chemotherapy. This review will highlight the stem cell based anti-cancer therapy targeting pancreatic cancer stem cells and different molecular signaling pathways. A particular focus will be on the therapeutic potential of naïve Stem cells, anti-cancer drug loaded stem cells, genetically engineered stem cells and exosomal miRNA released by stem cells in pancreatic cancer treatment. Similarly, the role of nanotechnology in stem cell based anticancer therapy will be further discussed to better implementation of these cell-based cancer therapy.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC.

Pancreatic cancer has an exaggerated dependence on mitochondrial metabolism, but methods to specifically target the mitochondria without off target effects in normal tissues that rely on these organelles is a significant challenge. The mitochondrial uncoupling protein 2 (UCP2) has potential as a cancer-specific drug target, and thus, we will review the known biology of UCP2 and discuss its potential role in the pathobiology and future therapy of pancreatic cancer.

To evaluate comparative outcomes of pancreatic cancer resection with or without adjuvant chemotherapy in patients with stage I pancreatic cancer.

A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without adjuvant chemotherapy were included, and their risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool. Survival outcomes were analyzed using the hazard ratio and odds ratio for the time-to-event and dichotomous outcomes, respectively.

We included 6 comparative studies reporting a total of 6,874 patients with resected stage 1 pancreatic cancer, of whom 3,951 patients had no adjuvant chemotherapy, and the remaining 2,923 patients received adjuvant chemotherapy. The use of adjuvant chemotherapy was associated with significantly higher overall survival (hazard ratio 0.71, 95% confidence interval 0.62-0.82, P < .00001) and 2-year survival (65.1% vs 57.4%, odds ratio 1.99; 95% confidence interval 1.01-1.41, P = .04) compared to no use of adjuvant chemotherapy. However, there was no statistically significant difference in 1-year (86.8% vs 78.4%, odds ratio 1.60; 95% confidence interval 0.72-3.57, P = .25), 3-year (46.0% vs 44.0%, odds ratio 1.07; 95% confidence interval 0.90-1.29, P = .43), or 5-year survival (24.8% vs 23.3%, odds ratio 1.03; 95% confidence interval 0.80-1.33, P = .81) between the 2 groups.

Meta-analysis of best available evidence (level 2a with low to moderate certainty) demonstrates that adjuvant chemotherapy may confer survival benefits for stage I pancreatic cancer when compared to the use of surgery alone. Randomized control trials are required to escalate the level of evidence and confirm these findings with consideration of contemporary chemotherapy agents and regimens.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death by 2030. The diagnosis at a late stage is the underlying cause for higher mortality and poor prognosis after surgery. Treatment resistance to chemotherapy and immunotherapy results in recurrence after surgery and poor prognosis. Neoantigen burden and CD8+ T-cell infiltration are associated with clinical outcomes in PDAC and paucity of neoantigen-reactive tumor-infiltrating lymphocytes may be the underlying cause for treatment resistance for immunotherapy. This suggests a need to identify additional neoantigens and therapies targeting these neoantigens to improve clinical outcomes in PDAC. In this review, we focus on describing the pathophysiology, current treatment strategies, and treatment resistance in PDAC followed by the need to target neoantigens in PDAC.

Background: Pancreatic cancer (PaC) is a highly malignant gastrointestinal tumor with invasive and metastatic characteristics. Interleukin-6 (IL-6), a negative prognostic marker, contributes to PaC progression. However, the mechanism of IL-6 in PaC is not yet fully understood. Methods: miR-455-5p levels were first tested by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in PaC tissues or cells. Subsequently, PaC cell-related functions were identified through CCK-8, Transwell, and Western blotting. Changes in miR-455-5p and IGF-1R expression were confirmed using RT-qPCR and Western blotting. miR-455-5p methylation was assessed by bisulfite sequencing PCR. Results: The authors discovered that miR-455-5p was expressed at low levels in PaC tissues and cells, and miR-455-5p expression was observably reduced by IL-6 in PaC cells. In addition, IL-6 dramatically induces miR-455-5p methylation in PaC cells. Functionally, the data revealed that IL-6 could facilitate the malignant properties of PaC cells, including proliferation, epithelial-mesenchymal transition, and metastasis. The authors found that miR-455-5p could suppress the progression of PaC cells by downregulating IGF-1R in PaC cells. Mechanistically, IL-6 downregulated miR-455-5p and upregulated IGF-1R, and miR-455-5p reduced IGF-1R expression through targeted binding. Conclusions: The authors demonstrated that the miR-455-5p/IGF-1R axis is necessary for the induction of IL-6 in PaC progression. The results here may provide a theoretical basis for the application of the IL-6/miR-455-5p/IGF-1R axis in the clinical therapy of PaC.

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.

Compared to traditional small molecule and antibody drugs, RNA-based drugs offer a simple design, short research and development cycles, high specificity, broad treatment fields, and long-term efficacy. As a result, RNA-based drugs are extensively used to treat genetic diseases, tumors, viral infections, and other illnesses, suggesting that they have the potential to become the third-largest drug class after small molecule and antibody drugs. Currently, more than 10 small nucleic acid drugs have gained regulatory approval. The commercialization successes of small nucleic acid drugs will stimulate the development of RNA-based drugs. Small nucleic acid drugs primarily target liver diseases, metabolic diseases, genetic diseases, and tumors, and there is also significant potential for expanding indications in the future. This review provides a brief overview of the advantages and development of small nucleic acid-based therapeutics and shows a focus on platform technologies such as chemical modifications and delivery systems that have enabled the clinical translation of small nucleic acid-based therapeutics. Additionally, we summarize the latest clinical progress in small nucleic acid-based therapeutics for the treatment of various diseases, including rare diseases, liver diseases, metabolic diseases, and tumors. Finally, we highlight the future prospects for this promising treatment approach.

We investigated the tumor suppression effect of an ultrasound-sensitive doxorubicin-loaded liposome-based nanoparticle, IMP301, to enhance the synergistic effect with focused ultrasound (FUS) in an animal model of pancreatic cancer.

Thirty nude mice with xenografts of PANC-1 human pancreatic cancer cells were randomly and prospectively allocated to 6 different groups (5 per group) each for Study-1 (dose-response test) and Study-2 (synergistic effect test). Study-1 consisted of control, gemcitabine, Doxil with FUS, and three different doses of IMP301 (2, 4, 6 mg/kg) with FUS groups. Study-2 consisted of control, FUS only, gemcitabine, Doxil with FUS, and IMP301 (4 mg/kg) with or without FUS groups. Differences in tumor volume and growth rate were evaluated by one-way ANOVA and Student-Newman-Keuls test.

In Study-1, 4 mg/kg or greater IMP301 with FUS groups showed lower tumor growth rates of 14 ± 4 mm3/day (mean ± standard deviation) or less, compared to the control, gemcitabine, and Doxil with FUS groups with rates exceeding 28 ± 5 (p < 0.050). The addition of FUS in Study-2 decreased the tumor growth rate in the IMP301-treated groups from 36 ± 17 to 9 ± 6, which was lower than the control, FUS only, gemcitabine, and Doxil with FUS groups (p < 0.050).

IMP301 combined with FUS exhibited higher tumor growth suppression compared to the use of a conventional drug alone or the combination with FUS. The present study showed the potential of IMP301 to enhance the synergistic effect with FUS for the treatment of pancreatic cancer.

This article aims to evaluate the synergistic effect of FUS and ultrasound-responsive liposomal drug in tumor growth suppression by using xenograft mouse model of pancreatic ductal adenocarcinoma. FUS-induced ultrasound-sensitive drug release may be a potential noninvasive repeatable treatment option for patients with locally advanced or unresectable pancreatic cancer.

• Modification of conventional drugs combined with FUS would maximize tumor suppression. • IMP301 with FUS had higher tumor suppression effect compared to conventional chemotherapy. • This image-guided drug delivery would enhance therapeutic effects of systemic chemotherapy.