Epigenetic deregulation of the COX pathway in cancer

Inflammation is a major cause of cancer and may condition its progression. The deregulation of the cyclooxygenase (COX) pathway is implicated in several pathophysiological processes, including inflammation and cancer. Although, its targeting with nonsteroidal antiinflammatory drugs (NSAIDs) and COX-...

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Bibliographic Details
Published in:Progress in lipid research 2012-10, Vol.51 (4), p.301-313
Main Authors: Cebola, Inês, Peinado, Miguel A.
Format: Article
Language:English
Subjects:
Dinoprost - biosynthesis
Dinoprostone - biosynthesis
DNA methylation
Epigenesis, Genetic
Epoprostenol - biosynthesis
Gene regulation
Gene Silencing
Histone modification
Humans
Inflammation and cancer
Neoplasms - enzymology
Neoplasms - pathology
Prostaglandin D2 - biosynthesis
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandins
Signal Transduction
Thromboxane A2 - biosynthesis
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Summary:Inflammation is a major cause of cancer and may condition its progression. The deregulation of the cyclooxygenase (COX) pathway is implicated in several pathophysiological processes, including inflammation and cancer. Although, its targeting with nonsteroidal antiinflammatory drugs (NSAIDs) and COX-2 selective inhibitors has been investigated for years with promising results at both preventive and therapeutic levels, undesirable side effects and the limited understanding of the regulation and functionalities of the COX pathway compromise a more extensive application of these drugs. Epigenetics is bringing additional levels of complexity to the understanding of basic biological and pathological processes. The deregulation of signaling and biosynthetic pathways by epigenetic mechanisms may account for new molecular targets in cancer therapeutics. Genes of the COX pathway are seldom mutated in neoplastic cells, but a large proportion of them show aberrant expression in different types of cancer. A growing body of evidence indicates that epigenetic alterations play a critical role in the deregulation of the genes of the COX pathway. This review summarizes the current knowledge on the contribution of epigenetic processes to the deregulation of the COX pathway in cancer, getting insights into how these alterations may be relevant for the clinical management of patients.
ISSN:0163-7827
1873-2194
DOI:10.1016/j.plipres.2012.02.005