From Scripps: “Scientists Show Commonly Prescribed Painkiller Slows Cancer Growth”

Scripps
Scripps Research Institute

June 06, 2016
By Eric Sauter

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have found that one of the most widely prescribed pain and anti-inflammation drugs slows the growth rate of a specific kind of cancer in animal models and suggests the medication could have the same effect on other types of tumors.

The new study, published online ahead of print by the journal Cancer Research, focused on the effects of celecoxib (Pfizer’s Celebrex®).

Celebrex® targets an enzyme called “cyclooxygenase-2” (COX-2), which is linked to pain and inflammation. This enzyme is also critical in the creation of prostaglandins, compounds that act like hormones and play a role in promoting tumor growth. COX-2 expression is typically low in normal tissue, but high in multiple types of cancers.

“We were actually interested in determining what a particular signaling pathway does in cancer,” said TSRI Associate Professor Joseph Kissil, who led the study. “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 Celebrex® inhibit.”

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Authors of the new study included (left to right) Smitha Kota, William Guerrant, Joseph Kissil, Scott Troutman and Vinay Mandati.

The researchers went on to conduct animal studies tracking the effects of celecoxib on the growth of cancer cells from a tumor type known as neurofibromatosis type II (NF2). In humans, NF2 is a relatively rare inherited form of cancer caused by mutations in the anti-tumor gene NF2, which leads to benign tumors of the auditory nerve.

Animals received a daily dose of the drug, and tumor growth was followed by imaging. Analysis of the results showed a significantly slower tumor growth rate in celecoxib-treated models than in controls.

Using various approaches, the new study also showed that a signaling cascade known as the Hippo-YAP pathway is involved in these results and that the protein YAP is required for the proliferation and survival of NF2 cells and tumor formation.

“Our study shows that COX2 inhibitors do have an effect on the tumor cells,” said TSRI Research Associate William Guerrant, the study’s first author. “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.”

In addition to Kissil and Guerrant, other authors of the study, “YAP Mediates Tumorigenesis in Neurofibromatosis Type 2 by Promoting Cell Survival and Proliferation through a COX-2–EGFR Signaling Axis,” are Smitha Kota, Scott Troutman, Vinay Mandati and Mohammad Fallahi of TSRI; and Anat Stemmer-Rachamimov of Massachusetts General Hospital.

The work was supported by the National Institutes of Health (grants NS077952 and CA124495). Guerrant is also a recipient of a Young Investigator Award from the Children’s Tumor Foundation.

See the full article here .

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The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.