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Review
. 2009 Jun;13(6):675-88.
doi: 10.1517/14728220902915567. Epub 2009 May 2.

Targeting the eicosanoid pathway in non-small-cell lung cancer

Leora Horn  1 , Michael Backlund, David H Johnson
Affiliations
Review

Targeting the eicosanoid pathway in non-small-cell lung cancer

Leora Horn et al. Expert Opin Ther Targets. 2009 Jun.

Abstract

Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) upregulation is an early event in the development of non-small-cell lung cancer. Preclinical data indicate tumors with upregulation of COX-2 synthesize high levels of prostaglandin E₂ (PGE₂), which in turn are associated with increased production of proangiogenic factors and enhanced metastatic potential. These findings indicate that an increase in COX-2 expression may play a significant role in the development and growth of lung cancers and possibly with the acquisition of an invasive and metastatic phenotype. Consequently, inhibitors of COX-2 are being studied for their chemopreventative and therapeutic effects in individuals at high risk for lung cancer and patients with established cancers.

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Figures

Figure 1
Figure 1
Arachidonic acid metabolism leading to the generation of eicosanoids.
Figure 2
Figure 2
Pre- and post-celecoxib PGE-M levels in never, former, and current smokers. PGE-M levels were quantified by liquid chromatography/electrospray ionization MS using selected reaction monitoring. Precision of the assay is ±5% and accuracy is 92%. Columns, means.
Figure 3
Figure 3
The increased understanding that selective COX-2 inhibitors are not free of unwanted side effects (particularly on renal and cardiovascular systems) have led to a reevaluation of other potential targets in the PG synthesis pathway downstream of COX for treatment and/or prevention of lung cancers, including PGE synthases and 15-PGDH. Another attractive target for inhibition of the activity of the PG synthesis pathway is inhibition of downstream receptor signaling.
Figure 4
Figure 4
Total RNA and protein were isolated from six individual human non-small cell lung cancer tissues and matched normal mucosa. Equal amounts of RNA and protein were analyzed for 15-PGDH expression. SCC = squamous cell carcinoma. N, normal lung; T, tumor tissue.
Figure 5
Figure 5
Photograph of the lungs from mice after tail vein injection of 3LL cells with or without treatment of the host with the EP4 antagonist ONO-AE3-208.
See this image and copyright information in PMC

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