JWCI Researchers Identify Epigenomic Test That Could Improve Treatment For Specific Gastric Cancers

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Cancer / Oncology
Article Date: 13 Dec 2007 - 2:00 PDT

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A study by researchers at the John Wayne Cancer Institute at Saint John's Health Center in a recent issue of Journal of Clinical Oncology identifies activation of the enzyme COX-2 in gastric cancer tumors as a prognostic indicator for poor outcome. The study suggests that inhibiting COX-2 with readily available drugs may improve outcomes for some gastric cancer patients.

The study, "Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer," retrospectively examined results on Cyclooxygenase-2 (COX-2) gene activation from 179 patients in the well-known D1D2 randomized multi-center clinical trial on surgical interventions in gastric cancer by the Dutch Gastric Cancer Group (Leiden). The new study was the first to look at epigenetic change for COX-2 in gastric tumors as an indicator for disease outcome and found tumors with COX-2 methylation (a DNA change that essentially stops or reduces COX-2 production) had significantly better survival rates. "The expression of COX-2 can be stopped with anti-COX-2 medications like specific types of non-steroidal anti-inflammatory drugs," an important prevention strategy says Dr. Dave S.B. Hoon, Director of Molecular Oncology at JWCI and senior author on the study. "Gastric tumors can be tested to determine whether there is COX-2 methylation or not and in the future be stratified into specific treatment regimens."

The activation of COX-2 by tumors can activate inflammation and other events that promote tumor progression. In gastric cancer, COX-2 has been found to assist in the development and progression of the cancer by increasing angiogenesis (the formation of blood vessels that feed the tumor), invasiveness, and metastasis.

Worldwide, stomach cancer is one of the most common causes of cancer deaths and the third most common cancer, according to the International Agency on Cancer Research (part of the World Health Organization). While gastric cancer rates in the U.S. have decreased since refrigeration and better food preservations in the 1930's, studies show rates have been increasing more in southern California compared to other parts of the USA. This is believed to be related to the increasing number of immigrants from some Latin American and Asian countries (the Philippines, China, Japan, and Korea) where stomach cancer rates remain high. Unfortunately, as an accompanying editorial in the Journal of Oncology notes, progress against gastric cancer has been "painfully slow" and nearly 60% of those diagnosed with the disease end up dying from it.

As an interesting side note, John Wayne - in whose honor the JWCI was founded - died of gastric cancer in 1979.

Hoon noted that COX-2 remains a significant research interest for all gastrointestinal cancers, and that previous studies have suggested COX-2 inhibition can play a role in colon cancer prevention. The current study, which continues a strong collaboration between JWCI and the Dutch Gastric Cancer Group at Leiden, is one of the largest biomarker studies to date relating COX-2 and gastric cancer. "It is the first to suggest an epigenetic biomarker for gastric cancer progression," he added.

Funding for this study was provided by the Martin H. Weil laboratory at JWCI, the Rod Fasone Memorial Fund at JWCI and the Drie Lichten Foundation in Leiden, The Netherlands.

Since 1981, the John Wayne name has been committed by the Wayne family to groundbreaking cancer research and education in memory of their father who died of cancer. The John Wayne Cancer Institute at Saint John's Health Center has received worldwide acclaim for advances in melanoma (skin cancer), breast and colon cancer as well as immune therapy of cancer. Other areas of research include prostate and liver cancer. Their unique ability to rapidly turn scientific breakthroughs into innovative approaches to treatment and early detection provides immediate hope to cancer patients from around the globe.

Michael F.G. de Maas, Cornelius J.H. van de Velde, Naoyuki Umetani, Pieter de Heer, Hein Putter, Anneke Q. van Hoesel, Gerrit A. Meijer, Nicole C. van Grieken, Peter J.K. Kuppen, Anton J. Bilchik, Rob A.E.M. Tollenaar and Dave S.B. Hoon, "Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer," Journal of Clinical Oncology, Volume26, Number 21, November 1, 2007, pp 4887-4894.

John Wayne Cancer Institute

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