Cancer and Metastasis Reviews

, Volume 37, Issue 2–3, pp 385–395 | Cite as

Eicosanoids and HB-EGF/EGFR in cancer

  • Cheng-Chieh Yang
  • Kuo-Wei ChangEmail author


Eicosanoids are bioactive lipids that play crucial roles in various pathophysiological conditions, including inflammation and cancer. They include both the COX-derived prostaglandins and the LOX-derived leukotrienes. Furthermore, the epidermal growth factor receptor (EGFR) pathways family of receptor tyrosine kinases also are known to play a central role in the tumorigenesis. Various antitumor modalities have been approved cancer treatments that target therapeutically the COX-2 and EGFR pathways; these include selective COX-2 inhibitors and EGFR monoclonal antibodies. Research has shown that the COX-2 and epidermal growth factor receptor pathways actively interact with each other in order to orchestrate carcinogenesis. This has been used to justify a targeted combinatorial approach aimed at these two pathways. Although combined therapies have been found to have a greater antitumor effect than the administration of single agent, this does not exempt them from the possible fatal cardiac effects that are associated with COX-2 inhibition. In this review, we delineate the contribution of HB-EGF, an important EGFR ligand, to the cardiac dysfunction related to decreased shedding of HB-EGF after COX-2/PGE2 inhibition. A better understanding of the molecular mechanisms underlying these cardiac side effects will make possible more effective regimens that use the dual-targeting approach.


Arachidonic acid Eicosanoids EGFR Cancer 


Funding information

This work was supported by grants MOST-105-2314-B-010-029-MY3 from the Ministry of Science and Technology and MOHW106-TDU-B-211-113001 from the Ministry of Health and Welfare of Taiwan.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Oral BiologyNational Yang-Ming UniversityTaipeiTaiwan
  2. 2.School of DentistryNational Yang-Ming UniversityTaipeiTaiwan
  3. 3.Department of StomatologyTaipei Veterans General HospitalTaipeiTaiwan

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