Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/138520
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Type: | Journal article |
Title: | Overcoming the Fibrotic Fortress in Pancreatic Ductal Adenocarcinoma: Challenges and Opportunities |
Author: | Myo Min, K.K. Ffrench, C.B. Jessup, C.F. Shepherdson, M. Barreto, S.G. Bonder, C.S. |
Citation: | Cancers, 2023; 15(8):1-19 |
Publisher: | MDPI AG |
Issue Date: | 2023 |
ISSN: | 2072-6694 2072-6694 |
Statement of Responsibility: | Kay K. Myo Min, Charlie B. Ffrench, Claire F. Jessup, Mia Shepherdson, Savio George Barreto, and Claudine S. Bonder |
Abstract: | An overabundance of desmoplasia in the tumour microenvironment (TME) is one of the defining features that influences pancreatic ductal adenocarcinoma (PDAC) development, progression, metastasis, and treatment resistance. Desmoplasia is characterised by the recruitment and activation of fibroblasts, heightened extracellular matrix deposition (ECM) and reduced blood supply, as well as increased inflammation through an influx of inflammatory cells and cytokines, creating an intrinsically immunosuppressive TME with low immunogenic potential. Herein, we review the development of PDAC, the drivers that initiate and/or sustain the progression of the disease and the complex and interwoven nature of the cellular and acellular components that come together to make PDAC one of the most aggressive and difficult to treat cancers. We review the challenges in delivering drugs into the fortress of PDAC tumours in concentrations that are therapeutic due to the presence of a highly fibrotic and immunosuppressive TME. Taken together, we present further support for continued/renewed efforts focusing on aspects of the extremely dense and complex TME of PDAC to improve the efficacy of therapy for better patient outcomes. |
Keywords: | pancreatic ductal adenocarcinoma; tumour microenvironment; desmoplasia; immunotherapy; targeted therapy |
Rights: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/) |
DOI: | 10.3390/cancers15082354 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT202100 |
Published version: | http://dx.doi.org/10.3390/cancers15082354 |
Appears in Collections: | Medicine publications |
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hdl_138520.pdf | Published version | 1.3 MB | Adobe PDF | View/Open |
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