» Articles » PMID: 39001498

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

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2024 Jul 13
PMID 39001498
Authors
Affiliations
Soon will be listed here.
Abstract

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

Citing Articles

Dissecting macrophage heterogeneity and kaempferol in lung adenocarcinoma: a single-cell transcriptomic approach and network pharmacology.

Wan L, Hao W, Li L, Wang L, Song Y Discov Oncol. 2025; 16(1):104.

PMID: 39884998 PMC: 11782783. DOI: 10.1007/s12672-025-01832-9.


A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs.

Neidle S Molecules. 2024; 29(15).

PMID: 39125057 PMC: 11314571. DOI: 10.3390/molecules29153653.

References
1.
Elyada E, Bolisetty M, Laise P, Flynn W, Courtois E, Burkhart R . Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts. Cancer Discov. 2019; 9(8):1102-1123. PMC: 6727976. DOI: 10.1158/2159-8290.CD-19-0094. View

2.
Canon J, Rex K, Saiki A, Mohr C, Cooke K, Bagal D . The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019; 575(7781):217-223. DOI: 10.1038/s41586-019-1694-1. View

3.
Larionova I, Cherdyntseva N, Liu T, Patysheva M, Rakina M, Kzhyshkowska J . Interaction of tumor-associated macrophages and cancer chemotherapy. Oncoimmunology. 2019; 8(7):1596004. PMC: 6527283. DOI: 10.1080/2162402X.2019.1596004. View

4.
Truong L, Pauklin S . Pancreatic Cancer Microenvironment and Cellular Composition: Current Understandings and Therapeutic Approaches. Cancers (Basel). 2021; 13(19). PMC: 8507722. DOI: 10.3390/cancers13195028. View

5.
Cao Y . Adipocyte and lipid metabolism in cancer drug resistance. J Clin Invest. 2019; 129(8):3006-3017. PMC: 6668696. DOI: 10.1172/JCI127201. View