Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2438 - 2438

Published: July 2, 2024

Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) tumor-associated macrophages (TAMs), contribute growth, angiogenesis, immune evasion. Although cells infiltrate TME, evade responses by secreting chemokines expressing checkpoint inhibitors (ICIs). Vascular components, like endothelial pericytes, stimulate angiogenesis support while adipocytes secrete factors that promote cell invasion, Additionally, perineural characteristic feature of PDAC, contributes local recurrence Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible (HIF), Wnt/β-catenin drive Targeting the TME is crucial for developing effective therapies, strategies inhibiting CAFs, modulating response, disrupting blocking neural interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve prognostic biomarkers targets personalized therapy.

Language: Английский

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Reprogramming the tumor microenvironment by targeting cytidine deaminase in pancreatic ductal adenocarcinoma tumors: implications for the role of P2Y6 receptors

Purinergic Signalling, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract Immunotherapies, such as immune checkpoint inhibitors (ICI), anti-cancer vaccines and adoptive T cell transfer, are promising treatments for cancer patients. However, ICI have not shown therapeutic benefit most mismatch repair-proficient colorectal pancreatic ductal adenocarcinoma tumors (PDAC), which aggressive deadly (Li et al. in Biomedicines 12:2175, 2024). Tumor metabolism can enhance immunological tolerance, but hinder function. In a recent publication Nature Cancer , Scolaro (Scolaro 5:1206–1226, 2024) showed that cytidine deaminase (CDA) upregulation may play crucial role shaping the immunosuppressive landscape of human PDAC other tumors. CDA targeting lines led to reduced tumor growth, weight total regression after treatment aimed at programmed death protein 1 receptor (PD-1) protein. inhibition, both genetically pharmacologically, overcame immunotherapy resistance models. cells altered microenvironment (TME), enabling respond anti-PD-1. mice with sgNT sgCda receiving anti-PD-1 treatment, they number CD8 + cells. reduction makes more sensitive immunotherapy, presumably by overcoming tumor-associated macrophages (TAMs) forcing them adopt an immunostimulatory phenotype. The study also found produce TME rich UDP (and UTP) taking advantage CDA-mediated pyrimidine salvage pathway. This setting inhibits recruitment activation promoting infiltration characteristics P2Y 6 receptor–expressing TAMs.

Language: Английский

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Borax Pentahydrate as a Promising Boron-Based Angiogenesis Inhibitor

Journal of Trace Elements in Medicine and Biology, Journal Year: 2025, Volume and Issue: 89, P. 127640 - 127640

Published: April 5, 2025

Language: Английский

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Unlocking the potential of chimeric antigen receptor T cell engineering immunotherapy: Long road to achieve precise targeted therapy for hepatobiliary pancreatic cancers

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139829 - 139829

Published: Jan. 13, 2025

Language: Английский

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Exploring the role of antigen-presenting cancer-associated fibroblasts and CD74 on the pancreatic ductal adenocarcinoma tumor microenvironment

Medical Oncology, Journal Year: 2024, Volume and Issue: 42(1)

Published: Nov. 25, 2024

Language: Английский

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