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Stroma-targeting strategies in pancreatic cancer: a double-edged sword

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with limited treatment options and terrible long-term survival, and it is expected to become the second leading cause of cancer-related death by 2030. One reason why this cancer is so aggressive and resistant is the formation of dense stroma that surrounds the neoplastic epithelium, which promotes tumor progression, invasion, metastasis, and resistance. The three major components of PDAC stroma are extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and vasculature. The dense ECM acts as a natural physical barrier, impeding drug penetration to PDAC tumor cells. Consequently, the method that combines stroma-targeting with anticancer therapy may be a viable alternative for increasing drug penetration. Additionally, blood vessels are key entities of the tumor stroma, serving as a pathway for nutrition as well as the only way for chemical medicines and immune cells to act. Finally, PDAC CAFs and tumor cells have crosstalk effects in the tumor microenvironment, where they are responsible for enhanced matrix deposition. In this review, we aim to provide an overview of our current comprehension of the three key components of PDAC stroma and the new promising therapeutic targets for PDAC.

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Funding

This research was funded by by China Scholarship Council to XL; La Ligue Contre le Cancer, INCa, Canceropole PACA and INSERM to JI; INSERM to PSC.

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  1. Centre de Recherche en Cancérologie de Marseille (CRCM), UMR 7258, INSERM U1068, CNRS, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique Et Technologique de Luminy, 163 Avenue de Luminy, 13288, Marseille, France

    Xi Liu, Juan Iovanna & Patricia Santofimia-Castaño

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  1. Xi Liu
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Correspondence to Patricia Santofimia-Castaño.

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Key Points

• PDAC is a deadly cancer characterized by a dense and extensive stromal matrix.

• The complex stromal components have brought great challenges to PDAC therapy.

• Stroma-targeting strategies will be prospective for the successful therapy of PDAC.

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Liu, X., Iovanna, J. & Santofimia-Castaño, P. Stroma-targeting strategies in pancreatic cancer: a double-edged sword. J Physiol Biochem 79, 213–222 (2023). https://doi.org/10.1007/s13105-022-00941-1

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