An Emerging Role for the Unfolded Protein Response in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one of the leading causes of cancer-associated deaths in the world. It is characterised by dismal response rates to conventional therapies. A major challenge in treatment strategies for PDAC is the presence of a...

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Bibliographic Details
Published in:Cancers 2021-01, Vol.13 (2), p.261
Main Authors: Robinson, Claire M, Talty, Aaron, Logue, Susan E, Mnich, Katarzyna, Gorman, Adrienne M, Samali, Afshin
Format: Article
Language:English
Subjects:
Adenocarcinoma
Autophagy
Cancer therapies
Chemotherapy
Cytokines
Endoplasmic reticulum
Extracellular matrix
Fibroblasts
Growth factors
Homeostasis
Medical prognosis
Metabolism
Metastasis
Microenvironments
Morphology
Mutation
Pancreatic cancer
Paracrine signalling
Pathogenesis
Phosphatase
Protein folding
Proteins
Review
Smooth muscle
Stellate cells
Tumor microenvironment
Tumorigenesis
Tumors
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Summary:Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one of the leading causes of cancer-associated deaths in the world. It is characterised by dismal response rates to conventional therapies. A major challenge in treatment strategies for PDAC is the presence of a dense stroma that surrounds the tumour cells, shielding them from treatment. This unique tumour microenvironment is fuelled by paracrine signalling between pancreatic cancer cells and supporting stromal cell types including the pancreatic stellate cells (PSC). While our molecular understanding of PDAC is improving, there remains a vital need to develop effective, targeted treatments. The unfolded protein response (UPR) is an elaborate signalling network that governs the cellular response to perturbed protein homeostasis in the endoplasmic reticulum (ER) lumen. There is growing evidence that the UPR is constitutively active in PDAC and may contribute to the disease progression and the acquisition of resistance to therapy. Given the importance of the tumour microenvironment and cytokine signalling in PDAC, and an emerging role for the UPR in shaping the tumour microenvironment and in the regulation of cytokines in other cancer types, this review explores the importance of the UPR in PDAC biology and its potential as a therapeutic target in this disease.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13020261