Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance
| Autor: | Paul Timpson, David Herrmann, Brooke A. Pereira, Cecilia R. Chambers, Kendelle J. Murphy |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Stromal cell extracellular matrix pancreatic cancer Review biomechanics Metastasis 03 medical and health sciences 0302 clinical medicine Stroma Pancreatic cancer stroma Medicine tumor microenvironment RC254-282 Tumor microenvironment business.industry Cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Desmoplasia 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Cancer-Associated Fibroblasts medicine.symptom business cancer-associated fibroblasts stromal targeting |
| Zdroj: | Cancers Cancers, Vol 13, Iss 3481, p 3481 (2021) |
| ISSN: | 2072-6694 |
| Popis: | Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies, with a five-year survival rate of only ~10%. Pancreatic tissue becomes increasingly fibrotic (known as desmoplasia) during cancer development and progression. This extensive, heterogeneous reaction is largely mediated through the actions of stromal cells such as cancer-associated fibroblasts (CAFs). In this review, we will discuss how heterotypical reciprocal tumor-stromal and tumor-immune cell interactions in the pancreatic tumor microenvironment (TME) can both promote and restrain PDAC development and progression, with particular focus on the role of extracellular matrix (ECM) in potentiating tumor cell proliferation, survival, metastasis, and treatment resistance. We also give a snapshot of the current and emerging stromal co-therapies used in combination with chemotherapy or immunotherapy to treat this highly deadly disease. Abstract Many cancer studies now recognize that disease initiation, progression, and response to treatment are strongly influenced by the microenvironmental niche. Widespread desmoplasia, or fibrosis, is fundamental to pancreatic cancer development, growth, metastasis, and treatment resistance. This fibrotic landscape is largely regulated by cancer-associated fibroblasts (CAFs), which deposit and remodel extracellular matrix (ECM) in the tumor microenvironment (TME). This review will explore the prognostic and functional value of the stromal compartment in predicting outcomes and clinical prognosis in pancreatic ductal adenocarcinoma (PDAC). We will also discuss the major dynamic stromal alterations that occur in the pancreatic TME during tumor development and progression, and how the stromal ECM can influence cancer cell phenotype, metabolism, and immune response from a biochemical and biomechanical viewpoint. Lastly, we will provide an outlook on the latest clinical advances in the field of anti-fibrotic co-targeting in combination with chemotherapy or immunotherapy in PDAC, providing insight into the current challenges in treating this highly aggressive, fibrotic malignancy. |
| Databáze: | OpenAIRE |
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