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.