Prognostic utility of TME-associated genes in pancreatic cancer DOI Creative Commons
Yuanhua Nie,

Longwen Xu,

Zilong Bai

et al.

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 1, 2023

Background: Pancreatic cancer (PC) is a deadly disease. The tumor microenvironment (TME) participates in PC oncogenesis. This study focuses on the assessment of prognostic and treatment utility TME-associated genes PC. Methods: After obtaining differentially expressed TME-related genes, univariate multivariate Cox analyses least absolute shrinkage selection operator (LASSO) were performed to identify related prognosis, risk model was established evaluate scores, based Cancer Genome Atlas (TCGA) data set, it validated by external sets from Gene Expression Omnibus (GEO) Clinical Proteomic Tumor Analysis Consortium (CPTAC). Multiomics adopted explore potential mechanisms, discover novel targets, assess sensitivities immunotherapy chemotherapy. Results: Five namely, FERMT1, CARD9, IL20RB, MET, MMP3, identified score formula constructed. Next, their mRNA expressions verified normal pancreatic cells. Multiple algorithms confirmed that displayed reliable ability prognosis prediction an independent factor, indicating high-risk patients had poor outcomes. Immunocyte infiltration, gene set enrichment analysis (GSEA), single-cell all showed strong relationship between immune mechanism low-risk samples. could predict sensitivity some chemotherapy regimens, which included oxaliplatin irinotecan. Various latent targets (LAG3, TIGIT, ARID1A) addressed mutation landscape model. Conclusion: can reflect functions as biomarkers for therapy.

Language: Английский

Therapeutic resistance to anti-oestrogen therapy in breast cancer DOI
Marie Will, Jackson Liang, Ciara Metcalfe

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(10), P. 673 - 685

Published: July 27, 2023

Language: Английский

Citations

62
Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review DOI Creative Commons

Rexiati Ruze,

Jianlu Song,

Xinpeng Yin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 24, 2023

Abstract Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers. The growing interest in this area is prominently actuated by the increasing obesity DM prevalence, which partially responsible slight but constant increase pancreatic cancer (PC) occurrence. PC a highly lethal malignancy characterized its insidious symptoms, delayed diagnosis, devastating prognosis. intricate process of promoting involves their local impact pancreas concurrent whole-body systemic changes that are suitable initiation. main mechanisms involved include excessive accumulation various nutrients metabolites directly while also aggravating mutagenic carcinogenic metabolic disorders affecting multiple pathways. Detrimental alterations gastrointestinal sex hormone levels microbiome dysfunction further compromise immunometabolic regulation contribute to establishment an immunosuppressive tumor microenvironment (TME) carcinogenesis, can be exacerbated several crucial pathophysiological processes TME components, such autophagy, endoplasmic reticulum stress, oxidative epithelial-mesenchymal transition, exosome secretion. This review provides comprehensive critical analysis DM-related dissects how impair anticancer immunity influence favor

Language: Английский

Citations

39
Barriers and opportunities in pancreatic cancer immunotherapy DOI Creative Commons

Yixin Ju,

Dongzhi Xu,

Miao-Miao Liao

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Sept. 12, 2024

Language: Английский

Citations

11
Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer DOI Creative Commons
Mingjie Wang,

Wenxiang Xue,

Hanghang Yuan

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2823 - 2849

Published: March 1, 2024

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

Language: Английский

Citations

10
Cancer-associated fibroblasts: A key target to snatch victory from defeat in therapy resistance associated with the pancreatic cancer stroma DOI
Wenhao Luo, Taiping Zhang

Cancer Letters, Journal Year: 2023, Volume and Issue: 567, P. 216279 - 216279

Published: June 17, 2023

Language: Английский

Citations

19
Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma DOI Creative Commons
Ann Mary Joseph,

Ahmad Al Aiyan,

Basel K. al-Ramadi

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 7, 2024

One of the most deadly and aggressive cancers in world, pancreatic ductal adenocarcinoma (PDAC), typically manifests at an advanced stage. PDAC is becoming more common, by year 2030, it expected to overtake lung cancer as second greatest cause cancer-related death. The poor prognosis can be attributed a number factors, including difficulties early identification, probability curative radical resection, limited response chemotherapy radiotherapy, its immunotherapy resistance. Furthermore, extensive desmoplastic stroma that surrounds forms mechanical barrier prevents vascularization promotes immune cell penetration. Phenotypic heterogeneity, drug resistance, immunosuppressive tumor microenvironment are main causes aggressiveness. There complex dynamic interaction between cells with stromal within tumour microenvironment. suppressive aggressiveness contributed range cellular humoral which itself modulated cancer. In this review, we describe role innate adaptive cells, PDAC, immune-mediated therapeutic advances, recent clinical trials PDAC.

Language: Английский

Citations

8
Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging DOI Creative Commons
Rita Saúde-Conde, Ayça Arçay, Kosta Stosic

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 591 - 591

Published: March 6, 2024

Pancreatic ductal adenocarcinoma (PDAC) represents a formidable challenge due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) in PDAC, characterized by intense stromal desmoplastic reactions dominant presence of cancer-associated fibroblasts (CAFs), significantly contributes therapeutic resistance. However, within the heterogeneous CAF population, fibroblast activation protein (FAP) emerges as promising target for Gallium-68 FAP inhibitor positron emission tomography (Ga68FAPI-PET) imaging. Notably, 68Ga-FAPI-PET demonstrates diagnostic sensitivity specificity, especially conjunction with low tracer uptake non-tumoral tissues. Moreover, it provides valuable insights into tumor–stroma interactions, critical aspect PDAC tumorigenesis not adequately visualized through conventional methods. clinical implications this innovative imaging modality extend potential reshape treatment strategies offering deeper understanding dynamic TME. while is evident, ongoing correlative studies are essential elucidate full spectrum heterogeneity validate impact on management. This article comprehensive review explores disease

Language: Английский

Citations

6
Roles of differently polarized macrophages in the initiation and progressionof pancreatic cancer DOI Creative Commons
Peter Störz

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 11, 2023

During development of pancreatic cancer macrophage-mediated inflammatory processes and the formation cancerous lesions are tightly connected. Based on insight from mouse models we provide an overview functions classically-activated pro-inflammatory alternatively-activated anti-inflammatory macrophages in initiation progression cancer. We highlight their roles earliest events tumor such as acinar-to-ductal metaplasia (ADM), organization fibrotic lesion microenvironment, growth low-grade (LG) lesions. then discuss tumor-associated (TAM) to high-grade (HG) with a invasive phenotype immunosuppressive microenvironment. Another focus is how targeting these macrophage populations can affect immunosuppression, fibrosis responses chemotherapy, eventually this knowledge could be used for novel therapy approaches patients ductal adenocarcinoma (PDA).

Language: Английский

Citations

15
Breaking the stromal barrier in pancreatic cancer: Advances and challenges DOI

Mohana Chakkera,

Jeremy B. Foote, Batoul Farran

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1879(1), P. 189065 - 189065

Published: Dec. 30, 2023

Language: Английский

Citations

14
Intratumoral T-cell receptor repertoire composition predicts overall survival in patients with pancreatic ductal adenocarcinoma DOI Creative Commons
Vikram S. Pothuri, Graham D. Hogg, Leah Conant

et al.

OncoImmunology, Journal Year: 2024, Volume and Issue: 13(1)

Published: March 15, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that refractory to immune checkpoint inhibitor therapy. However, intratumoral T-cell infiltration correlates with improved overall survival (OS). Herein, we characterized the diversity and antigen specificity of PDAC receptor (TCR) repertoire identify novel immune-relevant biomarkers. Demographic, clinical, TCR-beta sequencing data were collated from 353 patients across three cohorts underwent surgical resection for PDAC. TCR was calculated using Shannon Wiener index, Inverse Simpson "True entropy." Patients clustered by shared specificity. TCRs predictive OS identified their associated transcriptional states single-cell RNAseq. In multivariate Cox regression models controlling relevant covariates, high predicted multiple cohorts. Conversely, in peripheral blood, abundance T-cells, but not diversity, OS. Clustering based on revealed subset predicts Interestingly, these sequences more likely encode CD8

Language: Английский

Citations

5