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PTUPB: A Key to Hindering Tumor Inflammation

Epoxide hydrolase enzyme.

Although chemotherapy is a potent treatment, it sometimes causes dying cancer cells to become inflamed, triggering the growth of more malignant cells. Researchers have discovered a new anti-inflammatory compound that decreases tumor inflammation and reduces cancer growth in ovarian tumors in mice.

In these recent developments, published in Proceedings of the National Academy of Sciences, investigators discovered that first-line platinum- and taxane-based chemotherapies fuel a macrophage-derived "surge" of proinflammatory cytokines and bioactive lipids, thereby increasing tumor growth. Administering PTUPB, a dual lipid pathway inhibitor, hindered cyclooxygenase-2 (COX-2)—an enzyme that promotes inflammation—and soluble epoxide hydrolase (sHE)—an enzyme involved in metabolic processes in the liver—which in turn prohibited tumor inflammation and growth.

In previous studies, PTUPB has been shown to impede growth in breast and lung tumors.

"The drug is being clinically evaluated for its therapeutic properties in other diseases," commented one of the study's authors, Bruce Hammock, PhD, Professor in the Department of Entomology and Nematology at the University of California (UC) Davis and in the university's Comprehensive Cancer Center.

"To prevent tumor recurrence after therapy, it will be critical to neutralize the inherent tumor-promoting activity of therapy-generated debris," commented first author Allison Gartung, PhD, of Harvard Medical School and Beth Israel Deaconess Medical Center. "Our results indicate that a dual COX-2/sEH inhibitor may offer a novel alternative to protect the body from a debris-mediated inflammatory response."

This research is prompting further investigation into the efficacy of PTUPB as a cancer-treatment drug.

"We are exploring all options to translate PTUPB to cancer patients, especially in combination with current cancer therapies such as chemotherapy, radiation, immunotherapy, or surgery, which either directly or indirectly may generate tumor cell debris," remarked senior author Dipak Panigraphy, MD, of Harvard Medical School. "Our next step is to investigate whether our findings are consistent with clinical studies involving human cancer."

For More Information

Gartung A, Yang J, Sukhatme VP, et al (2019). Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2sEH inhibitor. Proc Natl Acad Sci USA. [Epub ahead of print] DOI:10.1073/pnas.1803999116

Image courtesy of Jawahar Swaminathan

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