Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions

Strapcova, Sabina; Takacova, Martina; Csaderova, Lucia; Martinelli, Paola; Lukacikova, Lubomira; Gal, Viliam; Kopacek, Juraj; Svastova, Eliska

doi:10.3390/cancers12082005

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Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions

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Department of Tumor Biology, Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovakia

Institute of Cancer Research, Clinic of Internal Medicine I, Medical University of Vienna, 1090 Vienna, Austria

Cancer Cell Signaling, Boehringer-Ingelheim RCV Vienna, A-1121 Vienna, Austria

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Alpha Medical Pathology, Ruzinovska 6, 82606 Bratislava, Slovakia

Author to whom correspondence should be addressed.

Cancers 2020, 12(8), 2005; https://doi.org/10.3390/cancers12082005

Received: 22 June 2020 / Revised: 14 July 2020 / Accepted: 16 July 2020 / Published: 22 July 2020

(This article belongs to the Special Issue New Insights into Tumour pH Regulation)

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Abstract

Hypoxia is a common phenomenon that occurs in most solid tumors. Regardless of tumor origin, the evolution of a hypoxia-adapted phenotype is critical for invasive cancer development. Pancreatic ductal adenocarcinoma is also characterized by hypoxia, desmoplasia, and the presence of necrosis, predicting poor outcome. Carbonic anhydrase IX (CAIX) is one of the most strict hypoxia regulated genes which plays a key role in the adaptation of cancer cells to hypoxia and acidosis. Here, we summarize clinical data showing that CAIX expression is associated with tumor necrosis, vascularization, expression of Frizzled-1, mucins, or proteins involved in glycolysis, and inevitably, poor prognosis of pancreatic cancer patients. We also describe the transcriptional regulation of CAIX in relation to signaling pathways activated in pancreatic cancers. A large part deals with the preclinical evidence supporting the relevance of CAIX in processes leading to the aggressive behavior of pancreatic tumors. Furthermore, we focus on CAIX occurrence in pre-cancerous lesions, and for the first time, we describe CAIX expression within intraductal papillary mucinous neoplasia. Our review concludes with a detailed account of clinical trials implicating that treatment consisting of conventionally used therapies combined with CAIX targeting could result in an improved anti-cancer response in pancreatic cancer patients. View Full-Text

Keywords: carbonic anhydrase IX; pancreatic cancer; intraductal papillary mucinous neoplasia; acidic microenvironment; hypoxia; correlation analysis; immunohistochemistry

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Strapcova, S.; Takacova, M.; Csaderova, L.; Martinelli, P.; Lukacikova, L.; Gal, V.; Kopacek, J.; Svastova, E. Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions. Cancers 2020, 12, 2005. https://doi.org/10.3390/cancers12082005

AMA Style

Strapcova S, Takacova M, Csaderova L, Martinelli P, Lukacikova L, Gal V, Kopacek J, Svastova E. Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions. Cancers. 2020; 12(8):2005. https://doi.org/10.3390/cancers12082005

Chicago/Turabian Style

Strapcova, Sabina, Martina Takacova, Lucia Csaderova, Paola Martinelli, Lubomira Lukacikova, Viliam Gal, Juraj Kopacek, and Eliska Svastova. 2020. "Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions" Cancers 12, no. 8: 2005. https://doi.org/10.3390/cancers12082005

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Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions

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