Novel approach to suppressing therapy-induced tumor growth and recurrence

Following up on a groundbreaking 2018 study in which BIDMC’s Dipak Panigrahy, MD, demonstrated that dead and dying cancer cells killed by conventional cancer treatments paradoxically trigger inflammation that promotes tumor growth and metastasis, a new study led by Allison Gartung, PhD, describes a novel approach to suppressing chemotherapy-induced tumor growth in an ovarian cancer model. Gartung and colleagues’ findings were published in published in January in Proceedings of the National Academy of Science (PNAS).

Working in a mouse model of the disease, the team confirmed that chemotherapy-killed ovarian cancer cells induce surrounding immune cells called macrophages to release a surge of chemicals. Together, these chemicals, known as cytokines and lipid mediators, create an environment conducive to tumor growth and survival.

“Conventional cancer therapy is a double-edged sword — the very treatment meant to control cancer is also helping it to survive and grow,” said Gartung, a postdoctoral fellow in BIDMC’s Department of Pathology. “To prevent tumor recurrence after therapy, it is critical to neutralize the inherent tumor-promoting activity of therapy-generated debris.”

Next, the team showed that a newly synthesized anti-inflammatory drug called PTUPB — specifically designed to target the chemical pathways that lead to cytokines and lipid mediators — blocks the debris-stimulated surge of tumor-promoting chemicals by macrophages. In addition, the scientists found that PTUPB prolonged survival in mice bearing ovarian tumors and suppressed debris-stimulated tumor growth.

“The role of these chemotherapy-induced cytokines and lipids is underappreciated and poorly characterized, and ovarian cancer patients may benefit from suppressing their release,” said Panigrahy, Assistant Professor of Pathology and a Scientist at the Cancer Center at BIDMC. “Further research is needed but, our results indicate that PTUPB may complement conventional cancer therapies by acting as a ‘surge protector’ against cell debris-stimulated tumor growth.”

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Story Source:

Materials provided by Beth Israel Deaconess Medical Center. Note: Content may be edited for style and length.

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Journal Reference:

1. Allison Gartung, Jun Yang, Vikas P. Sukhatme, Diane R. Bielenberg, Djanira Fernandes, Jaimie Chang, Birgitta A. Schmidt, Sung Hee Hwang, David Zurakowski, Sui Huang, Mark W. Kieran, Bruce D. Hammock, Dipak Panigrahy. Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2/sEH inhibitor. Proceedings of the National Academy of Sciences, 2019; 201803999 DOI: 10.1073/pnas.1803999116

https://www.sciencedaily.com/releases/2019/01/190115111953.htm