A widely prescribed pain and anti-inflammation medication, celecoxib (Celebrex; Pfizer), reduced the growth of neurofibromatosis type 2 (NF2) tumors in mice and in cell cultures. These results suggest that celecoxib could reduce tumor growth in some types of cancer.1
In people, NF2 is a rare, heritable type of cancer caused by mutations in the anticancer gene NF2. The resulting tumors are benign and located on the auditory nerve.
This study, published in Cancer Research, found that a downstream target of the Hippo-YAP pathway, which is involved in tumor development in many different types of cancer, is cyclooxygenase-2 (COX-2).
COX-2 is an enzyme involved in pain and inflammation. It is also important for the generation of prostaglandins, which act similarly to hormones and promote tumor growth. Usually, COX-2 expression is low in normal tissue and high in some cancer tissues.
“We were actually interested in determining what a particular signaling pathway does in cancer,” explained Joseph Kissil, PhD, associate professor, Department of Cancer Biology, the Scripps Research Institute, Jupiter, Florida, and the study leader.
“In the process, we found that it activates genes that promote survival of tumor cells and that they do so by turning on enzymes involved in inflammation, including COX2, which anti-inflammatory drugs like [celecoxib] inhibit.”
Researchers then used a mouse model of NF2 to measure the effects of celecoxib on tumorigenesis. They administered a daily dose of celecoxib to the mice and followed tumor growth with imaging. Results showed tumor growth rate was significantly reduced in mice that received celecoxib compared with controls.
“Our study shows that COX2 inhibitors do have an effect on the tumor cells,” said William Guerrant, PhD, research associate, the Scripps Research Institute, and first author of the study.
“They also have an impact on inflammatory responses that play a role in tumor growth. It’s possible that in other cancers these effects might actually be stronger because of the drug’s impact on inflammation.”
1. Guerrant W, Kota S, Troutman S, et al. YAP mediates tumorigenesis in neurofibromatosis type 2 by promoting cell survival and proliferation through a COX-2–EGFR signaling axis [published online May 23, 2016]. Cancer Res. doi:10.1158/0008-5472.CAN-15-1144