National Colorectal Cancer Research Alliance
EIF’s NCCRA funding supports cutting-edge research at several leading institutions conducted by world-class scientists working on prevention, diagnostic tools, treatment, and, ultimately, a cure for colorectal cancer:
Dennis J. Slamon, M.D., Ph.D
Jonsson Comprehensive Cancer Center
David Geffen School of Medicine at UCLA
With EIF seed funding, Dr. Dennis Slamon’s research at the Jonsson Cancer Center at UCLA focused on studying specific genetic alterations associated with the development and progression of colorectal cancer. By focusing on a specific area of the chromosome associated with colon cancer, called 20-q, Dr. Slamon and his team have identified ten possible candidate genes that could potentially play significant roles in colon cancer. These findings could lead to new approaches in the treatment of colorectal cancer. Another example of Dr. Slamon’s effort was the work done on assessing Avastin, a growth inhibitor in cancer cells, which led to the first clinical translational study evaluating its efficacy on colon cancer patients. In addition, EIF funding was used to help establish the community-based Clinical Cancer Research Network at UCLA, which provides Dr. Slamon and his team the critically important systems to translate new and innovative ideas into clinical testing.
Raymond DuBois, M.D., Ph.D
M.D. Anderson Cancer Center
University of Texas
With EIF seed funding, Dr. Raymond DuBois’s research – initially at Vanderbilt University Medical Center and now at M.D. Anderson Cancer – has focused on developing better options for the prevention and early detection of colon cancer. Dr. Dubois and his team evaluated the role of prostaglandins such as PGE2, a signaling molecule produced by cancer cells in very high levels, and identified several new genes regulated by it. One of those genes is called NR4A2, which has been shown to be instrumental in controlling cancer cell death. Another newly identified gene called GROalpha was shown to inhibit colorectal tumor growth upon activation. These findings could be potentially important clinically because antibodies directed against these genes may be useful for the treatment of patients with colorectal cancer. According to Dr. Dubois, carrying out this kind of experiment is very high risk and would not be supported by other funding mechanisms. Thus, the support from EIF has been crucial.
Robert J. Mayer, M.D.
Dana Farber Cancer Institute
Harvard Medical School
With EIF seed funding, Dr. Robert Mayer and his team at Harvard Medical School have focused on improving access and compliance for colorectal cancer screening through a program called “Open Doors to Health.” The program is a randomized controlled trial being conducted in 12 low-income housings sites in the metropolitan Boston area with the goal of determining how best to increase colon cancer screening and prevention among diverse, low-income communities. Colonoscopic examinations are being offered at two major Boston medical centers. As of November, 2005, 1548 residents of the housing sites have been recruited. In addition, Dr. Mayer and his research group established a minority tumor bank, so that polyps and other biopsies can be stored and screened for comparative analysis among the different ethnic groups. These findings may determine whether colorectal cancer in one ethnic group is biologically identical to that in others.
Anil Rustgi, M.D.
G.I. Division & Abramson Cancer Center
University of Pennsylvania School of Medicine
With EIF seed funding, Dr. Anil Rustgi’s research at the University of Pennsylvania, Abramson Cancer Center and Department of Medicine (GI division), focused on the identification and implementation of new diagnostic biomarkers for the detection of colon polyps and colon cancer. Dr. Rustgi has begun to recognize patterns of proteins in blood samples of animal models that mimic human colon cancer, and is applying to see if similar patterns exist in patients at average-risk and high-risk for colon cancer. This approach is called “proteomics,” the study of proteins, which can lead to the development of new screening techniques using only blood samples for the diagnosis of colon cancer. In addition, Dr. Rustgi and his team have identified new genes that are involved in the progression of colon polyps and colon cancer such as ParvinBeta and ARHGAP8, which regulate the ability of colon cancer cells to migrate and invade. These new gene discoveries can have great impact on the knowledge and therapy of colon cancer.
Bert Vogelstein, M.D.
Howard Hughes Medical Institute and
Johns Hopkins Kimmel Cancer Center
Dr. Vogelstein is widely recognized for his discovery of the genes that, when altered, cause colon cancer. With EIF seed funding, Dr. Vogelstein’s lab completed an exhaustive sequencing of more than 18,000 genes in a series of colon tumor samples. Collaborating with fellow NCCRA Medical Advisory Board member Sanford Markowitz, M.D., Ph.D, the team identified 140 gene mutations that are likely to give rise to colon cancer. With this knowledge, Dr. Vogelstein and his team have contributed to the development of a non-invasive test that can detect mutations in DNA purified from stool samples. The test has been proven to identify over 60% of patients with early, surgically curable colon cancers. In addition to these diagnostic applications, Dr. Vogelstein’s work is guiding the development of new therapies that specifically target the genetic mutations that can cause colon cancer.
Sanford Markowitz, M.D., Ph.D
Howard Hughes Medical Institute and
Case Western Reserve University School of Medicine
With EIF seed funding, Dr. Sanford Markowitz’s research at the Howard Hughes Medical Institute has recently focused on the genetic underpinnings of colon cancer metastasis. Building on the gene sequencing project Dr. Markowitz collaborated on with Dr. Vogelstein, he and his team compared metastatic colon cancer deposits to the colon tumors from which they originated. They found, surprisingly, that the same mutations found in the metastatic colon cancers were also present their “parent” colon tumors – i.e. metastases arise from colon tumors that are “hard wired” to spread. The next stage of the project compares the DNA of colon tumors in patients with metastatic disease to colon tumors from patients who don't experience metastases. Understanding the genetic defects that cause colorectal cancer to spread beyond the colon could highlight patients at high risk of metastases and help guide treatment decisions.
I. Bernard Weinstein, M.D.
Frode Jensen Professor of Medicine
With EIF seed funding, Dr. Bernard Weinstein has made exciting progress in identifying anticancer agents from natural plant products. He has obtained evidence that a specific chemical found in green tea called EGCG inhibits activity of the insulin-like growth factor (IGF-1R), which plays a critical role in the development of colorectal cancer. In another related study, Dr. Weinstein discovered that two chemicals isolated from garlic, SAMC and DADS, inhibits growth and induces apoptosis (cell death) in colon cancer cells by binding to and disrupting the function of microtubules, thereby blocking cell division. These findings, which identify chemicals in green tea and garlic that inhibit the growth of cancer cells, suggest new approaches to the prevention and treatment of colorectal cancer. As a result of Dr. Weinstein’s research, the National Cancer Institute has funded a randomized clinical trial at Columbia University to determine if an extract from green tea called Poly E might be useful in preventing the development of esophageal cancer in patients at increased risk for this disease. The findings from this study may be useful for the prevention and treatment of colon and other types of cancer.
Walter Willett, M.D., Dr.P.H.
Harvard School of Public Health
With EIF seed funding, Dr. Walter Willet’s research at Harvard School of Public Health focused in the area of colon cancer prevention. His findings strongly suggest that colon cancer is potentially preventable. Dr. Willet and his team set out to identify dietary and lifestyle variables that reduced the risk of colon cancer. This study was motivated by Asian and Latin American countries having lower rates of colon cancer as compared to the U.S. To accomplish this, Dr. Willet and his research group collected detailed information about diet, smoking intake, alcohol consumption, lifestyle factors, and family history of various cancers on over 200,000 women and 50,000 men, following them over time to see who developed cancer, in particular, colon cancer. As a result of this substantial data collection effort, Dr. Willett identified a series of diet and lifestyle changes that could have prevented 70% of colon cancer in this population. Increased levels of folic acids and vitamin-D are two of the most promising factors which could prevent colon cancer. Other factors include, being physically active and fit, avoid smoking, and reduce red meat consumption.
Bernard Levin, M.D.
Dr. Bernard Levine, whose research had been funded by the NCCRA from its inception, retired from his position as Vice-President of the Division of Cancer Prevention and Population Sciences at M.D. Anderson Cancer Center, University of Texas. He now serves as a member emeritus of the NCCRA scientific advisory board.
EIF’s NCCRA provided lead funding to open The Jay Monahan Center for Gastrointestinal Health at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, named in memory of Couric’s late husband, who died of colon cancer in 1998 at age 42. Lead by Director Mark B. Pochapin, MD., the center offers a unique model of service designed to promote gastrointestinal cancer prevention and provide state-of-the-art treatment and support to patients and their families facing a diagnosis of gastrointestinal cancer.