Treatment Of Pancreatic Cancer Research Articles

Abstract 2514: Adjuvant chemotherapy drug response-related gene detection using JASPAC01 pancreatic cancer resection cohort

Abstract Background of Purpose: Although various multidisciplinary treatments have been attempted for pancreatic cancer, sufficient improvement in prognosis has not been achieved. It is necessary to establish biomarkers that can predict the malignant potential for each patient and the therapeutic effect of chemotherapy in order to select the optimal treatment for each individual case.This study was designed as a companion study to the phase III comparative study (JASPAC 01 of gemcitabine (GEM) and S-1 therapy as adjuvant chemotherapy after pancreatectomy. Among the 22 candidate biomarker genes that have been reported to be involved in pancreatic cancer treatment prognosis, we focused on E2F transcription factor 7 (E2F7), which is associated with a significantly poor overall survival rate when highly expressed. E2F7 is one of the target proteins of p53 and has been reported to be involved in cell cycle regulation. We examined the possibility of E2F7 expression in pancreatic cancer surgery and the effect of adjuvant chemotherapy. Patients and Methods: After optimizing the E2F7 imunostaining protocol, we scored E2F7 protein expression using the slides from excised tissues from JASPAC 01 registered cases. We investigated the relationship between malignancy and treatment efficacy using the case cohort treatment allocation information, clinicopathological information, and prognosis data. Results: Immunostaining was performed on approximately 330 resected pancreatic cancer specimens from 24 facilities nationwide. Of the 311 patients for whom E2F7 protein expression could be scored, 202 patients who completed the assigned treatment were included in the analysis. In 88 cases with high E2F7 expression, no significant difference in clinicopathological factors was observed between the S-1 treatment group and the GEM treatment group, but the S-1 treatment group showed better recurrence-free survival (RFS, P=0.066) and overall survival (OS, P=0.015) were observed. On the other hand, in the 114 patients with low E2F7 expression, there was no significant difference in clinicopathological factors between the two groups (RFS, P=0.168, OS: P=0.276). High E2F7 expression in pancreatic cancer tissues may affect S-1 sensitivity, GEM resistance, or both. Conclusions: It is considered that high expression E2F7 in pancreatic cancer may affect the therapeutic efficacy of GEM and S-1, which are frequently used in adjuvant chemotherapy for pancreatic cancer. Citation Format: Yukiyasu Okamura, Tomohisa Otsu, Masamichi Hayashi, Ryo Ashida, Katsuhiko Uesaka. Adjuvant chemotherapy drug response-related gene detection using JASPAC01 pancreatic cancer resection cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2514.

The Italian registry of families at risk for pancreatic cancer (IRFARPC): implementation and evolution of a national program for pancreatic cancer surveillance in high-risk individuals.

Screening programs for early detection and treatment of pancreatic cancer (PC) and its precursor lesions are increasingly implemented worldwide to reduce disease-specific lethality. Given the relatively low prevalence of the disease, the ideal target of such approaches is an enriched cohort of individuals harboring a lifetime risk of developing PC significantly higher compared to the general population, given either a substantial aggregation of PC cases in their family (i.e. familial pancreatic cancer) or a genomic landscape enriched with pathogenic variants associated with pancreatic carcinogenesis (i.e. mutation carriers). In Italy, a national registry for the census and surveillance of high-risk individuals for PC was launched in 2015, enrolling some 1200 subjects as of today. In this perspective, the scientific background, multi-level structure, and evolution of IRFARPC are outlined, as well as its long-term results, future developments, and areas for improvement.

Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis

BackgroundProtein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood.Methods and resultsIn this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients.ConclusionThese investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.

The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is among the most penetrative malignancies affecting humans, with mounting incidence prevalence worldwide. This cancer is usually not diagnosed in the early stages. There is also no effective therapy against PDAC, and most patients have chemo-resistance. The combination of these factors causes PDAC to have a poor prognosis, and often patients do not live longer than six months. Because of the failure of conventional therapies, the identification of key biomarkers is crucial in the early diagnosis, treatment, and prognosis of pancreatic cancer. 65% of the human genome encodes ncRNAs. There are different types of ncRNAs that are classified based on their sequence lengths and functions. They play a vital role in replication, transcription, translation, and epigenetic regulation. They also participate in some cellular processes, such as proliferation, differentiation, metabolism, and apoptosis. The roles of ncRNAs as tumor suppressors or oncogenes in the growth of tumors in a variety of tissues, including the pancreas, have been demonstrated in several studies. This study discusses the key roles of some lncRNAs and miRNAs in the growth and advancement of pancreatic carcinoma. Because they are involved not only in the premature identification, chemo-resistance and prognostication, also their roles as potential biomarkers for better management of PDAC patients.

Long-term outcomes of combined treatment of primary resectable pancreatic head cancer in patients over 70 years

Aim. To evaluate long-term oncological outcomes of pancreatoduodenectomy in resectable pancreatic head cancer in patients over 70 years of age. Materials and methods. A retrospective analysis of the Moscow Clinical Scientific Center registry revealed 63 patients aged > 70 years with resectable pancreatic head cancer. In 2016–2023, these patients underwent pancreatoduodenectomy. Males accounted for 35 %, and the median age comprised 75 years. Stage II was diagnosed in 44.4 % of patients, stage I – in 31.7 %, and stage III – in 23.8 %. Median follow-up accounted for 34.5 months. The authors analyzed the effect of patient characteristics, tumor, perioperative data and method of surgery on overall survival. Results. Adjuvant chemotherapy (p = 0.005; HR 0.28, CI 0.115–0.62) and low preoperative albumin levels (p = 0.004; HR 0.203, CI 0.28–0.61) had a significant impact on overall survival. After open surgery, 56 % of patients did not receive adjuvant chemotherapy, after minimally invasive surgery – 15.4 % (p = 0.0001). Conclusion. Minimally invasive pancreatoduodenectomy reveals no negative effect on the oncological outcomes of treatment for resectable pancreatic head cancer in patients ≥ 70 years old. Adjuvant chemotherapy and hypoalbuminemia prior to surgery are considered to be statistically significant factors influencing overall survival. Minimally invasive techniques enable adjuvant chemotherapy to be administered to a larger number of patients compared to open intervention.

Assessment of quality of life in patients after surgery for pancreatic and periampullary malignancies. Systematic review

Aim. To analyze the current methods of life quality assessment in patients undergoing surgical treatment for pancreatic and periampullary cancer, to study the influence of surgical treatment and postoperative complications on the quality of life. Materials and methods. The study involves a systematic review of the literature available in MEDLINE, Embase and e-Library electronic databases for 2015–2022. The methodology of the systematic review is reflected in the study protocol, designed according to PRISMA guidelines. Results. The systematic review embraces 26 studies including 4937 patients met the inclusion criteria. The present study examines design and objectives, survey forms, methods of surgical interventions and drug treatment, survey frequency and data collection methodology, risk of systematic error, etc. Conclusion. When choosing a survey form, most authors favored EORTC QLQ-C30 and EORTC QLQ-PAN26. Even the most complex surgeries such as pancreaticoduodenal resection and pancreatectomy can provide a satisfactory quality of life. Many current studies appear methodologically-challenged thereby increasing the risk of systematic error and reducing the reliability of the data. The quality of life of patients in this category is to be further investigated, the optimal principles and methodology of such studies are to be standardized, in particular, in Russian healthcare system.

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria.

Traditional treatments for pancreatic cancer (PC) are inadequate. Photodynamic therapy (PDT) is non-invasive, and proven safe to kill cancer cells, including PC. However, the mitochondrial concentration of the photosensitizer, such as verteporfin, is key. To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs, post-PDT. Workable survival rates of PC cells (AsPC-1, BxPC-3) were determined with chemotherapy [doxorubicin (DOX) and gemcitabine (GEM)] and non-chemotherapy [sirolimus (SRL) and cetuximab (CTX)] drugs in vitro, with or without verteporfin, as measured via MTT, flow cytometry, and laser confocal microscopy. Reduced cell proliferation was associated with GEM that was more enduring compared with DOX. Confocal laser microscopy allowed observation of GEM- and verteporfin-treated PC cells co-stained with 4',6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin, respectively. Cell survival significantly dropped upon exposure to either chemotherapy drug, but not to SRL or CTX. Both cell lines responded similarly to GEM. The intensity of fluorescence was associated with the concentration of verteporfin. Additional experiments using GEM showed that survival rates of the PC cells treated with 10 μmol/L verteporfin (but not less) were significantly lower relative to nil verteporfin. Living and dead stained cells treated with GEM were distinguishable. After GEM treatment, verteporfin was observed primarily in the mitochondria. Verteporfin was observed in living cells. In GEM -treated human PC cells, verteporfin was particularly prevalent in the mitochondria. This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

Lifestyle Medicine for the Prevention and Treatment of Pancreatitis and Pancreatic Cancer.

The incidence of pancreatitis and pancreatic cancer is on the upswing in the USA. These conditions often lead to higher healthcare costs due to the complex nature of diagnosis and the need for specialized medical interventions, surgical procedures, and prolonged medical management. The economic ramification encompasses direct healthcare expenses and indirect costs related to productivity losses, disability, and potential long-term care requirements. Increasing evidence underscores the importance of a healthy lifestyle in preventing and managing these conditions. Lifestyle medicine employs evidence-based interventions to promote health through six key pillars: embracing a whole-food, plant-predominant dietary pattern; regular physical activity; ensuring restorative sleep; managing stress effectively; removing harmful substances; and fostering positive social connections. This review provides a comprehensive overview of lifestyle interventions for managing and preventing the development of pancreatitis and pancreatic cancer.

Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells.

Pancreatic cancer is a lethal disease, harboring a five-year overall survival rate of only 13%. Current treatment approaches thus require modulation, with attention shifting towards liberating the stalled efficacy of immunotherapies. Select chemotherapy drugs which possess inherent immune-modifying behaviors could revitalize immune activity against pancreatic tumors and potentiate immunotherapeutic success. In this study, we characterized the influence of gemcitabine, a chemotherapy drug approved for the treatment of pancreatic cancer, on tumor antigen presentation by human leukocyte antigen class I (HLA-I). Gemcitabine increased pancreatic cancer cells' HLA-I mRNA transcripts, total protein, surface expression, and surface stability. Temperature-dependent assay results indicated that the increased HLA-I stability may be due to reduced binding of low affinity peptides. Mass spectrometry analysis confirmed changes in the HLA-I-presented peptide pool post-treatment, and computational predictions suggested improved affinity and immunogenicity of peptides displayed solely by gemcitabine-treated cells. Most of the gemcitabine-exclusive peptides were derived from unique source proteins, with a notable overrepresentation of translation-related proteins. Gemcitabine also increased expression of select immunoproteasome subunits, providing a plausible mechanism for its modulation of the HLA-I-bound peptidome. Our work supports continued investigation of immunotherapies, including peptide-based vaccines, to be used with gemcitabine as new combination treatment modalities for pancreatic cancer.

Silver nanoparticles green-formulated by a medicinal plant for the treatment of pancreatic, colorectal, and gastric cancers

Pancreatic, colorectal, and gastric cancers are common cancers with severe clinical signs. Finding a new anticancer supplement or drug inside of the chemotherapeutic drug is valuable. We synthesized iron nanoparticles containing pomegranate fruit aqueous extract for investigating anti-pancreatic cancer, anti-colorectal cancer, and anti-gastric cancer, cytotoxicity, and antioxidant effects. The AgNPs synthesized using green formulation underwent characterization through FT-IR, UV–Vis, FE-SEM, TEM, EDX, and XRD techniques. The UV–Vis spectroscopy analysis revealed that the nanoparticles displayed peak absorption at around 442 nm. The peaks at 77.105, 64.205, 44.180, and 37.835 corresponding to silver nanoparticles (311), (220), (200), and (111) diffraction planes, indicate the AgNPs formation. The signals at energy of 2.64 and 3.02 keV are assigned for Ag Lα and Ag Lβ. The signals 0.27 (for C Lα) and 0.52 (O Lα) prove the secondary metabolites linkage of extract to the synthetic silver nanoparticles surface. In vitro experiments, after 3–4 passages, the cancer cells (colorectal carcinoma (Ramos.2G6.4C10 and HT-29), gastric cancer (KATO III and MKN45), and pancreatic cancer (MIA PaCa-2 and PANC-1)) and normal cell (HUVEC) were prepared in number and morphology terms. After separating the cells from the flask surface using trypsin-EDTA, the viability and count of the cells were evaluated. Subsequently, a total of 3 × 103 cells were cultured, with the option of including or excluding nanoparticles. IC50 of silver nanoparticles was 183, 209, 203, 218, 228, and 157 on Ramos.2G6.4C10, HT-29, KATO III, MKN45, MIA PaCa-2, and PANC-1 cancer cells. In this research, the maximum antioxidant effectiveness against DPPH was documented to be around 100 % when tested 1000 μg/ml.

Exosomal lncRNA XIST promotes perineural invasion of pancreatic cancer cells via miR-211-5p/GDNF.

Perineural invasion (PNI) is an essential form of tumor metastasis in multiple malignant cancers, such as pancreatic cancer, prostate cancer, and head and neck cancer. Growing evidence has revealed that pancreatic cancer recurrence and neuropathic pain positively correlate with PNI. Therefore, targeting PNI is a proper strategy for pancreatic cancer treatment. Exosomal lncRNA derived from pancreatic cancer cells is an essential component of the tumor microenvironment. However, whether exosomal lncXIST derived from pancreatic cancer cells can promote PNI and its exact mechanism remains to be elucidated. We show that lncXIST mediates nerve-tumor crosstalk via exosomal delivery. Our data reveal that exosomal lncXIST derived from pancreatic cancer cells is delivered to neural cells and promotes their release of glial-cell-line-derived neurotrophic factor (GDNF), essential in facilitating the PNI of pancreatic cancer. Mechanistically, microRNA-211-5p negatively regulates GDNF, and lncXIST serves as a miR-211-5p sponge. The function of exosomes in the dynamic interplay between nerves and cancer is confirmed in both in vivo and in vitro PNI models. Therefore, targeting pancreatic cancer cell-derived exosomal lncXIST may provide clues for a promising approach for developing a new strategy to combat PNI of pancreatic cancer.

Conquering chemoresistance in pancreatic cancer: Exploring novel drug therapies and delivery approaches amidst desmoplasia and hypoxia

Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a mere 10% survival rate at the 5-year mark, finding effective interventions becomes even more pressing. The intricate relationship between desmoplasia and hypoxia in the tumor microenvironment further complicates matters by promoting resistance to chemotherapy and impeding treatment efficacy. The dense extracellular matrix and cancer-associated fibroblasts characteristic of desmoplasia create a physical and biochemical barrier that impedes drug penetration and fosters an immunosuppressive milieu. Concurrently, hypoxia nurtures aggressive tumor behaviour and resistance to conventional therapies. a comprehensive exploration of emerging medications and innovative drug delivery approaches. Notably, advancements in nanoparticle-based delivery systems, local drug delivery implants, and oxygen-carrying strategies are highlighted for their potential to enhance drug accessibility and therapeutic outcomes. The integration of these strategies with traditional chemotherapies and targeted agents reveals the potential for synergistic effects that amplify treatment responses. These emerging interventions can mitigate desmoplasia and hypoxia-induced barriers, leading to improved drug delivery, treatment efficacy, and patient outcomes in pancreatic cancer. This review article delves into the dynamic landscape of emerging anticancer medications and innovative drug delivery strategies poised to overcome the challenges imposed by desmoplasia and hypoxia in the treatment of pancreatic cancer.

Design and synthesis of chitosan/calcium lignosulfonate/Au NPs: Its performance for reduction of nitro compounds and in the treatment of cancer

This work introduces the preparation of a novel type of crosslinked polymers support based on calcium lignosulfonate-chitosan (CLS-CS) hydrogel with capping/reducing ability to encapsulated gold nanoparticles (CLS-CS/Au NPs). The morphology, structure and physicochemical properties of the prepared nanoparticles were characterized by different analytical techniques such as FT-IR, FE-SEM, TEM, EDX-elemental mapping study. The obtained results shown that CLS-CS/Au NPs prepared as spherical particles with sizes of 20–30 nm. The CLS-CS/Au NPs was applied as well for reduction of nitroarenes. The reduction of nitroarenes was obtained with good to high yields within short times. The related nanocatalyst was recovered for eight runs without significant loss of its catalytic performance. The MTT examination was conducted to check the anti-pancreatic cancer, anti-gastric cancer, anti-colorectal carcinoma, and cytotoxicity efficacies of the treated cells with CLS-CS/Au NPs over a 48-hour period on normal (HUVEC) and cancer cells. The IC50 values of the CLS-CS/Au NPs were found to be 169 µg/mL for HT-29 (colorectal carcinoma cell), 196 µg/mL for MKN45 (Gastric cancer cell), and 112 µg/mL for PANC-1 (Pancreatic cancer cell). The growth of malignant colorectal, gastric and pancreatic cells was found to decrease in a dose-dependent manner when exposed to CLS-CS/Au NPs. Following clinical research, CLS-CS/Au NPs shows promise as an effective treatment for colorectal, gastric and pancreatic cancers.

Pancreatic Cancer Treatment Targeting the HGF/c-MET Pathway: The MEK Inhibitor Trametinib.

Pancreatic cancer is characterized by fibrosis/desmoplasia in the tumor microenvironment, which is primarily mediated by pancreatic stellate cells and cancer-associated fibroblasts. HGF/c-MET signaling, which is instrumental in embryonic development and wound healing, is also implicated for its mitogenic and motogenic properties. In pancreatic cancer, this pathway, along with its downstream signaling pathways, is associated with disease progression, prognosis, metastasis, chemoresistance, and other tumor-related factors. Other features of the microenvironment in pancreatic cancer with the HGF/c-MET pathway include hypoxia, angiogenesis, metastasis, and the urokinase plasminogen activator positive feed-forward loop. All these attributes critically influence the initiation, progression, and metastasis of pancreatic cancer. Therefore, targeting the HGF/c-MET signaling pathway appears promising for the development of innovative drugs for pancreatic cancer treatment. One of the primary downstream effects of c-MET activation is the MAPK/ERK (Ras, Ras/Raf/MEK/ERK) signaling cascade, and MEK (Mitogen-activated protein kinase kinase) inhibitors have demonstrated therapeutic value in RAS-mutant melanoma and lung cancer. Trametinib is a selective MEK1 and MEK2 inhibitor, and it has evolved as a pivotal therapeutic agent targeting the MAPK/ERK pathway in various malignancies, including BRAF-mutated melanoma, non-small cell lung cancer and thyroid cancer. The drug's effectiveness increases when combined with agents like BRAF inhibitors. However, resistance remains a challenge, necessitating ongoing research to counteract the resistance mechanisms. This review offers an in-depth exploration of the HGF/c-MET signaling pathway, trametinib's mechanism, clinical applications, combination strategies, and future directions in the context of pancreatic cancer.

FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel as First Line Treatment in Pancreatic Cancer: A Real-World Comparison.

Advanced pancreatic cancer has a poor prognosis and a 5-year survival rate <5%; thus, treatment of patients with advanced unresectable or metastatic disease is challenging. Current guidelines recommend either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FOL) as first-line treatment. Data on both efficacy and toxicity of FOL versus GnP in metastatic cancer are limited. This study aimed to compare the two chemotherapy regimens in terms of efficacy and toxicity in a real-world setting. This retrospective propensity score matching study reviewed the medical records of 123 consecutive patients with advanced or metastatic pancreatic cancer who received either GnP or FOL between March 2013 and January 2019 in Guglielmo da Saliceto Hospital, Piacenza. Fifty patients (40.65%) received FOL, administered in an attenuated dose, and seventy-three patients (59.35%) received GnP. After a propensity matching score, 100 patients were retrospectively evaluated. In the final matched cohort, there was no difference in neoadjuvant therapy, radiotherapy, and surgery performed before the first-line therapy between the two groups. Progression-free survival and overall survival were comparable between the two groups and no difference was found in the percentage of toxicity. There was no difference in outcomes between patients who received FOL and those who received GnP. Unexpectedly, no greater FOL-related toxicity was found, probably due to the dose reduction.

Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.

Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.

Targeted irradiation in an autochthonous mouse model of pancreatic cancer.

The value of radiotherapy in the treatment of pancreatic cancer has been the subject of much debate but limited preclinical research. We hypothesise that the poor translation of radiation research into clinical trials of radiotherapy in pancreatic cancer is due, in part, to inadequate preclinical study models. Here, we developed and refined methods for targeted irradiation in autochthonous mouse models of pancreatic cancer, using a small animal radiotherapy research platform. We tested and optimised strategies for administration of contrast agents, iohexol and the liver imaging agent Fenestra LC, to enable the use of computed tomography imaging in tumour localisation. We demonstrate accurate tumour targeting, negligible off-target effects and therapeutic efficacy, depending on dose, number of fractions and tumour size, and provide a proof of concept that precise radiation can be delivered effectively to mouse pancreatic tumours with a clinically relevant microenvironment. This advance will allow investigation of the radiation response in murine pancreatic cancer, discovery of mechanisms and biomarkers of radiosensitivity or resistance, and development of radiosensitising strategies to inform clinical trials for precision radiotherapy in this disease.

A real-world analysis of second-line treatment option, gemcitabine plus anlotinib and anti-PD1, in advanced pancreatic cancer

BackgroundIn the second-line treatment of advanced pancreatic cancer (APC), there is only one approved regimen based on the phase III NAPOLI-1 trial. However, for patients progressing after Nab-paclitaxel and Gemcitabine (Nab-P/Gem) or Nab-P combinations, second-line treatment were very limited. MethodsThis is a retrospective single-center analysis of patients. Our aim was to determine the effectiveness and tolerability of a novel regimen, gemcitabine plus Anlotinib and anti-PD1, in APC patients and to compare it with oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX) in the second-line setting who have failed on the first-line Nab-P combinations. ResultsIn total, twenty-three patients received Gemcitabine plus Anlotinib and anti-PD1 in the second-line, 28 patients were treated with FOLFORINOX. There was no significant difference in overall survival (OS) or progression free survival (PFS) for either of the two sequences (p > 0.05). Patients who received Gemcitabine plus Anlotinib and anti-PD1 had a median PFS of 4.0 months (95% CI: 1.1–6.9) versus 3.5 months (95% CI 1.8–5.2) in FOLFORINOX group (p = 0.953). The median OS of Gemcitabine plus Anlotinib and anti-PD1 was 9.0 months (95% CI: 4.0–13.7) and 8.0 months (95% CI: 5.5–10.5) in FOLFORINOX group (p = 0.373). Grade ≥3 treatment-emergent adverse events (AEs) occurred for 13% of patients with Gemcitabine plus Anlotinib and anti-PD1 and 40% for FOLFORINOX. ConclusionOur data confirms the effectiveness of Gemcitabine plus Anlotinib and anti-PD1 as a well-tolerated regimen in the second-line treatment of APC and extends available data on its use as a second-line treatment option when compared with FOLFIRINOX.

Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer.

Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.

Short-Term Outcomes of Conventional Laparoscopic versus Robot-Assisted Distal Pancreatectomy for Malignancy: Evidence from US National Inpatient Sample, 2005-2018.

The primary treatment for pancreatic cancer is surgical resection, and laparoscopic resection offers benefits over open surgery. This study aimed to compare the short-term outcomes of robot-assisted vs. conventional laparoscopic distal pancreatectomy. Data of adults ≥ 20 years old with pancreatic cancer who underwent conventional laparoscopic or robot-assisted laparoscopic distal pancreatectomy were extracted from the United States (US) Nationwide Inpatient Sample (NIS) 2005-2018 database. Comorbidities and complications were identified through the International Classification of Diseases (ICD) codes. Short-term outcomes were compared using logistic regression and included length of hospital stay (LOS), perioperative complications, in-hospital mortality, unfavorable discharge, and total hospital costs. A total of 886 patients were included; 27% received robot-assisted, and 73% received conventional laparoscopic surgery. The mean age of all patients was 65.3 years, and 52% were females. Multivariable analysis revealed that robot-assisted surgery was associated with a significantly reduced risk of perioperative complications (adjusted odds ratio (aOR) = 0.61, 95% confidence interval (CI): 0.45-0.83) compared to conventional laparoscopic surgery. Specifically, robot-assisted surgery was associated with a significantly decreased risk of VTE (aOR = 0.35, 95% CI: 0.14-0.83) and postoperative blood transfusion (aOR = 0.37, 95% CI: 0.23-0.61). Robot-assisted surgery was associated with a significantly shorter LOS (0.76 days shorter, 95% CI: -1.43--0.09) but greater total hospital costs (18,284 USD greater, 95% CI: 4369.03-32,200.70) than conventional laparoscopic surgery. Despite the higher costs, robot-assisted distal pancreatectomy is associated with decreased risk of complications and shorter hospital stays than conventional laparoscopic distal pancreatectomy.