Science Writers’ Symposium on COX-2

Cancer researchers at New York Weill Cornell Medical Center and Pharmacia, a global pharmaceutical company, recently co-sponsored a special seminar for science writers entitled, “From Arthritis to Cancer—A New View of Cox-2.” The event hosted various media including WABC-TV, Glamour magazine, Contemporary Surgery, Oncology Times, Drug Topics, and Drugstore News. 

What was clear from this symposium is that we have entered a new era in the fight against cancer. Over the past few years, medicine has achieved steady declines in cancer rates, primarily due to improved screening methods, surgical techniques and more effective therapies. But with the advent of new data on cyclooxygenase-2 (COX-2) inhibitors and ongoing trials in different areas of disease, chemoprevention of cancer may be close at hand.

A Novel Target for Cancer Prevention and Treatment
According to researchers at the symposium, discovering the most effective methods of prevention and treatment of cancer begins with achieving a better understanding of how disease develops in the human body. It is the key to identifying and controlling cancer before it strikes. “Cancer is a disease that does not suddenly happen in a moment, it develops over time,” explained Dr. Andrew Dannenberg, MD, “that is why there is a need for ongoing research in cancer prevention with particular focus on early detection and screening methods.” 

So why focus on COX-2? Researchers revealed that despite the decrease in overall cancer incidence and mortality rates in the United States over the past decade, cancer still remains a major public health problem, justifying the continued need for preclinical and clinical investigations to support novel, targeted cancer therapies. One such area of intense study is the role of COX-2 in cancer. COX-2 is an enzyme that is overexpressed in a variety of premalignant and malignant diseases, including gastrointestinal cancers, head and neck cancers, lung cancers, urologic malignancies, and breast cancer. However, compounds such as NSAIDs (nonsteroidal anti-inflammatory drugs), that inhibit cyclooxygenase, have demonstrated promise for prevention and treatment of these forms of cancers and many others, which is why a number of current studies are underway within major medical centers across the United States, including at NewYork- Presbyterian Hospital.

Cancer Research at Work
Significant progress has been made in understanding the ways in which NSAIDs block key mechanisms in the growth and development of various cancers. Until recently, NSAIDs were indicated primarily to provide pain relief and reduce the inflammation of arthritis, but current research has revealed that their impact may be more far reaching. 

COX-2 is a naturally occurring enzyme that mediates inflammation and pain in sites throughout the body, and also stimulates the production of prostaglandins. Prostaglandins are chemical messengers that have been detected in high levels in certain disease conditions, such as colon cancer. Their production has been linked to the ability of tumors to spread. NSAIDs work by blocking the COX enzyme, which initiates prostaglandin production. Recent investigations have shown that NSAIDs may prevent the chain of events that lead to the development of cancer cells. With this understanding, modern medicine has taken a closer look at a new class of anti-inflammatory medications, called COX inhibitors, in the treatment and prevention of cancer. In fact, celecoxib—a selective COX-2 inhibitor which has been touted as the leading osteoarthritis and adult rheumatoid arthritis medication—is the only pharmacologic agent to be approved in the United States as an adjunct therapy for a rare condition called familial adenomatous polyposis (FAP), a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colonic polyps develop. Researchers now believe that medications like celecoxib may make a significant difference in the treatment of many diseases. 

At NewYork-Presbyterian Hospital, research is underway to examine the efficacy and safety of celecoxib in the inhibition of tumor growth. In one study, investigators are attempting to determine whether celecoxib can prevent the recurrence of sporadic colorectal adenomas. In another trial, the potential utility of celecoxib is being evaluated in patients with lung cancer. Results from animal studies suggest that in conjunction with existing treatment measures, inhibition of COX-2 can reduce the rate of tumor growth and metastasis in many cases. And since anti-inflammatory agents are relatively inexpensive and do not cause side effects in most people, they hold tremendous potential for the chemoprevention of many forms of cancer. “The ability of celecoxib to block neoangiogenesis and suppress tumor growth suggests a novel application of this anti-inflammatory drug in the prevention and treatment of certain diseases,” suggested cancer study investigators Mark Pochapin, MD and Nasser Altorki, MD, “and that is why close examination of enzymes such as COX-2 is critical to learning how and why cancer develops.” 

Learning in the Lab
For a hands-on perspective of cancer research at work, symposium attendees were treated to a unique laboratory tour led by Kotha Subbaramaiah, PhD, who offered an in-depth tutorial of cancer progression and the methods by which researchers gather knowledge about disease. Participants were taken step-by-step through the investigative process, beginning with a microscopic view of COX-2 expression in cancerous human tissue. This revealing look at cancer development was followed by demonstration of cancer cell preservation and growth, and a glimpse into how COX-2 inhibitors can impact the progression of some forms of cancer. “Through research, scientists are acquiring a better understanding of why cancer cells grow and behave abnormally,” explained Dr. Subbaramaiah, “with this knowledge, we can design novel, effective therapies that are aimed at preventing and treating human cancer.”

As the search for the missing pieces to the NSAIDs–COX-2 puzzle continues, investigators say that demonstrating the significance of COX-2 in the development of certain cancers is just the beginning. The hope is that through greater understanding of the precise role of COX-2 in the progression and prevention of cancer, comprehensive research will ultimately lead to the use of highly specific drugs to stop disease in its tracks. 

Editor’s Note:
Andrew Dannenberg, MD, is Director of Cancer Prevention, New York Weill Cornell Medical Center, and Henry Erle, MD-Roberts Family Professor of Medicine, Weill Medical College of Cornell University.

Mark Pochapin, MD, is Director, Gastrointestinal Endoscopy, New York Weill Cornell Medical Center, and Associate Professor of Clinical Medicine, Weill Medical College of Cornell University.

Nasser Altorki, MD, is Director, Division of Thoracic Surgery, New York Weill Cornell Medical Center, and Professor of Cardiothoracic Surgery, Weill Medical College of Cornell University.

Kotha Subbaramaiah, PhD, is Assistant Professor of Medicine, Weill Medical College of Cornell University.