Assistant Professor of Oncology Iowa State University Ames, Iowa
Presentation Description / Session Abstract: Chronic immune activation and subsequent inflammation is known to stimulate the development of cancer. Exposure to an inciting cause results in the upregulation of non-specific pro-inflammatory cytokines and enzymes, the most important of which is the cyclooxygenase enzyme 2 (COX-2). The primary function of COX-2 is to convert arachidonic acid to prostaglandins. The most active and predominant product in this cascade is prostaglandin E2 (PGE2), which drives many physiological functions including cell proliferation, apoptosis, and angiogenesis. These functions have been utilized by cancer cells to support growth and progression of multiple human, canine, and feline malignancies. Thus, blockade of this cascade with COX-2 specific or non-specific COX-2 non-steroidal anti-inflammatories (NSAIDs) is a popular treatment strategy. However, preventing the effects of COX-2 and subsequent prostaglandin formation can result in significant off-target effects. Thus, alternative treatment strategies are necessary. The physiological effects of PGE2 are mediated through its four currently recognized receptors (EP1 receptor to EP4 receptor [EP1R-EP4R]) on the surface of the target cells. Concurrent with the upregulation of COX-2 and PGE2 in multiple cancers, it has also been found that EP receptors, specifically EP4R, are associated with the development of malignancy in several human and canine cancers. Thus, specific blockade of EP receptors may confer a more targeted, therapeutic advantage to our patients with cancer. This session will review the current clinical evidence for the use of NSAIDs in canine and feline cancer patients and the potential benefit of using a more targeted EP4R antagonist instead.
Understand the use of COX2 inhibition specifically for cancer patients.
Develop a working knowledge of the EP4 receptor and its role in cancer development.
Understand the role of an EP4 receptor antagonist in the treatment of some cancer patients.