Current and future immunotherapeutic approaches in pancreatic cancer treatment

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 4, 2024

Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.

Язык: Английский

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Sea Anemone-like Nanomachine Based on DNA Strand Displacement Composed of Three Boolean Logic Gates: Diversified Input for Intracellular Multitarget Detection

Analytical Chemistry, Год журнала: 2024, Номер 96(10), С. 4120 - 4128

Опубликована: Фев. 27, 2024

Efficient and accurate acquisition of cellular biomolecular information is crucial for exploring cell fate, achieving early diagnosis, the effective treatment various diseases. However, current DNA biosensors are mostly limited to single-target detection, with few complex logic circuits comprehensive analysis three or more targets. Herein, we designed a sea anemone-like nanomachine based on strand displacement composed gates (YES-AND-YES) delivered into cells using gold nano bipyramid carriers. The AND gate activation depends trigger chain released by upstream reactions, while output signal relies downstream DNAzyme structure. Under influence diverse inputs (including enzymes, miRNA, metal ions), interconnected simultaneously perform logical multiple targets, generating unique in YES/NO format. This sensor can successfully distinguish healthy from tumor be further used diagnosis different cells, providing promising platform cell-type identification.

Язык: Английский

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Overcoming Obstacles: The Role of Lipid Nanocarriers in Therapeutic Approaches for Pancreatic Cancer

BioNanoScience, Год журнала: 2025, Номер 15(2)

Опубликована: Март 11, 2025

Язык: Английский

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Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in gastric cancer

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 21, 2022

Introduction Cuproptosis is a novel identified regulated cell death (RCD), which correlated with the development, treatment response and prognosis of cancer. However, potential role cuproptosis-related genes (CRGs) in tumor microenvironment (TME) gastric cancer (GC) remains unknown. Methods Transcriptome profiling, somatic mutation, copy number alteration clinical data GC samples were downloaded from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database to describe alterations CRGs genetic transcriptional fields. Differential, survival univariate cox regression analyses carried out investigate GC. molecular subtypes by using consensus unsupervised clustering analysis based on expression profiles CRGs, further analyzed GO KEGG gene set variation (GSVA). Genes distinct also enrichment (GSEA). Differentially expressed (DEGs) screened analysis. Consensus prognostic DEGs was performed identify genomic subtypes. Next, patients randomly categorized into training testing group at ratio 1:1. CRG Risk scoring system constructed through logistic least absolute shrinkage selection operator (LASSO) analysis, multivariate validated combined groups. Real-time quantitative polymerase chain reaction (RT-qPCR) used evaluate key genes. Sensitivity specificity examined receiver operating characteristic (ROC) curves. pRRophetic package R therapeutic effects drugs high- low- risk score group. Finally, nomogram developed predict patients’ incorporating clinicopathological features score. Results Most up-regulated tissues showed relatively high mutation frequency. Survival revealed that LIAS FDX1 significantly associated survival. After classified two cuproptosis subtypes, (gender, age, grade TNM stage), prognosis, metabolic related pathways immune infiltration TME 84 DEGs, obtained primarily enriched regulation metabolism intracellular/extracellular structure Univariate 32 DEGs. According re-classified grade, T N stage, patients. Nest, moderate sensitivity specificity. A score, characterized decreased microsatellite instability-high (MSI-H), burden (TMB) stem (CSC) index, stromal TME, indicated poor Four five dysregulated compared normal samples. Moreover, greatly multiple drugs. we established highly accurate for promoting applicability system. Discussion Our comprehensive demonstrated their roles features, prognosis. These findings may improve our understanding provide new perceptions doctors develop more effective personalized therapy strategies.

Язык: Английский

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Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs

Drug Resistance Updates, Год журнала: 2023, Номер 71, С. 101002 - 101002

Опубликована: Авг. 22, 2023

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication available to provide potential clinical benefits. However, drug resistance big obstacle obtain desired prognosis. In this review, we summary treatment strategies mechanisms adenocarcinoma different including pancreatic cancer, gastric adenocarcinoma, colorectal lung prostate cancer. Although underlying molecular involved vary one organ other, there are several targets that universal targeting these molecules could potentially reverse adenocarcinomas.

Язык: Английский

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Next-generation therapies for pancreatic cancer

Expert Review of Gastroenterology & Hepatology, Год журнала: 2024, Номер 18(1-3), С. 55 - 72

Опубликована: Фев. 28, 2024

Introduction Pancreas ductal adenocarcinoma (PDAC) is a frequently lethal malignancy that poses unique therapeutic challenges. The current mainstay of therapy for metastatic PDAC (mPDAC) cytotoxic chemotherapy. NALIRIFOX (liposomal irinotecan, fluorouracil, leucovorin, oxaliplatin) an emerging standard care in the setting. An evolving understanding pathogenesis driving shift toward targeted therapy. Olaparib, poly-ADP-ribose polymerase (PARP) inhibitor, has regulatory approval maintenance BRCA-mutated mPDAC along with other agents receiving disease-agnostic approvals including rare fusions and mismatch repair deficiency. Ongoing research continues to identify evaluate expanding array therapies PDAC.

Язык: Английский

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Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression

Nature Cancer, Год журнала: 2024, Номер 5(2), С. 283 - 298

Опубликована: Янв. 9, 2024

Abstract Lipids and their modifying enzymes regulate diverse features of the tumor microenvironment cancer progression. The secreted enzyme autotaxin (ATX) hydrolyzes extracellular lysophosphatidylcholine to generate multifunctional lipid mediator lysophosphatidic acid (LPA) supports growth several types, including pancreatic ductal adenocarcinoma (PDAC). Here we show that ATX suppresses accumulation eosinophils in PDAC microenvironment. Genetic or pharmacologic inhibition increased number intratumor eosinophils, which promote cell apoptosis locally suppress Mechanistically, eosinophil via an autocrine feedback loop, wherein ATX–LPA signaling negatively regulates activity AP-1 transcription factor c-Jun, turn suppressing expression potent chemoattractant CCL11 (eotaxin-1). Eosinophils were identified human specimens, rare individuals with high abundance had longest overall survival. Together recent findings, this study reveals context-dependent, immune-modulatory potential cancer.

Язык: Английский

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Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth

Cancer Discovery, Год журнала: 2024, Номер 14(10), С. 1964 - 1989

Опубликована: Июль 3, 2024

Abstract Pancreatic cancer is characterized by an extensive fibroinflammatory microenvironment. During carcinogenesis, normal stromal cells are converted to cytokine-high cancer-associated fibroblasts (CAF). The mechanisms underlying this conversion, including the regulation and function of fibroblast-derived cytokines, poorly understood. Thus, efforts therapeutically target CAFs have so far failed. Herein, we show that signals from epithelial expressing oncogenic KRAS—a hallmark pancreatic mutation—activate fibroblast autocrine signaling, which drives expression cytokine IL33. Stromal IL33 remains high dependent on KRAS throughout carcinogenesis; in turn, environmental stress induces interleukin-33 (IL33) secretion. Using compartment-specific knockout mice, observed lack leads profound reprogramming multiple components tumor microenvironment, CAFs, myeloid cells, lymphocytes. Notably, loss increase CD8+ T-cell infiltration activation and, ultimately, reduced growth. Significance: This study provides new insights into programming shows during process, induced. CAF-derived has pleiotropic effects supporting its potential as a therapeutic target.

Язык: Английский

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Overcoming therapy resistance in pancreatic cancer: New insights and future directions

Biochemical Pharmacology, Год журнала: 2024, Номер 229, С. 116492 - 116492

Опубликована: Авг. 15, 2024

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

Язык: Английский

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The power and the promise of CAR-mediated cell immunotherapy for clinical application in pancreatic cancer

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from epithelial cells pancreatic duct and acinar cells. This particular neoplasm has highly unfavorable prognosis due its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, limited survival duration. Cellular immunotherapy ex vivo culture expansion immune effector cells, granting them capacity selectively target malignant using specialized techniques. Subsequently, these modified are reintroduced into patient's organism with purpose eradicating tumor providing therapeutic intervention for cancer. Present situation: Presently, primary cellular modalities employed in treatment cancer encompass CAR T-cell therapy, TCR NK-cell therapy. Review: review provides concise overview mechanisms targets associated various cell therapies. Additionally, we will explore prospective outlook therapy context treating

Язык: Английский

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