Key Link Responsible For Colon Cancer Initiation, Metastasis

“We have demonstrated that CXCR2 mediates a critical step in the setup of the blood circulatory machinery that feeds tumor tissue. This provides an important new clue for the development of therapeutic targets to neutralize the effect of CXCR2 on colon cancer.” The DuBois’ Laboratory for Inflammation and Cancer, which includes lead author Hiroshi Katoh, and colleagues Dingzhi Wang, Takiko Daikoku, Haiyan Sun, and Sudhansu K. Dey, published the results in the November 11 issue of Cancer Cell. The results provide critical new clues toward the prevention of colorectal cancer, the second leading cause of cancer deaths in the U.S. Despite the availability of colonoscopy screening, the 5-year survival rate remains low, due to a large number patients presenting with advanced stages of the disease. Currently, there are no clinically available blood tests for the early detection of sporadic colon cancer. Inflammation has long been associated with increasing one’s risk for colon cancer. For instance, more than 20 percent of patients with a form of inflammatory bowel disease (IBD) develop colorectal cancer within 30 years of diagnosis. This colitis-associated cancer has a slow progression, but a very poor response to treatment and a high mortality rate. Researchers have known that the broad mechanisms of cancer involve an interplay with the immune system response that includes: recruiting immune cells that influence the tumor microenvironment, escaping from host immunosurveillance and suppression, shifting of the host immune response, and tumor-associated angiogenesis to establish the blood supply. For the study, the research team first “knocked-out” or removed the CXCR2 gene in mice, and found that the signs typically associated with inflammation were prevented. Furthermore, they demonstrated that CXCR2 dramatically suppressed colonic inflammation and the colitis associated tumor formation, growth and progression in mice. CXCR2 decorates the outer part of immune cells called myeloid-derived suppressor cells, or MDSCs, that work to block the immune response of killer CD8+ T cells. In the knockout mice, without CXCR2 present, the MDSC cells could no longer migrate from the circulatory system to the colon, dodge the killer CD8+ T cell immune response, and feed the blood supply of the tumor environment.


Genomic Health Announces Colon Cancer Publication Supporting Wider Oncotype DX(R) Utilization

Two-thirds (67 percent) of changes in treatment recommendations were decreases in treatment intensity (changes from chemotherapy to observation or from oxaliplatin-containing chemotherapy to treatment with fluoropyrimidine monotherapy), while one-third (33 percent) of changes were increases in treatment intensity. “In the past, selection of stage II patients for chemotherapy treatment following surgery has been based on a limited set of clinical and pathologic markers that are uninformative for most patients,” said Thomas H. Cartwright, M.D., Florida Cancer Affiliates, Ocala, Florida, and the principal investigator of this study. “The Oncotype DX colon cancer test has been clinically validated to provide a quantitative, individualized Recurrence Score and has been very helpful in treatment planning. The test represents an important advancement in bringing personalized medicine into today’s clinical setting to benefit patients.” To read the publication titled “Effect of the 12-Gene Colon Cancer Assay Results on Adjuvant Treatment Recommendations in Patients with Stage II Colon Cancer,” visit: Separately, the Journal of Clinical Oncology accepted for publication positive results from the third successful validation of the Oncotype DX colon cancer test in patients with stage II disease and first validation study in patients with stage III disease. Presented at the 2012 European Society for Medical Oncology Congress, these findings demonstrate that incorporation of the Recurrence Score may better inform adjuvant therapy decisions for certain patients with stage III disease, as well as those with stage II colon cancer. About Genomic Health Genomic Health, Inc. (NASDAQ: GHDX) is the world’s leading provider of genomic-based diagnostic tests that address the overtreatment of early stage cancer, one of the greatest issues in healthcare today. The company is applying its world-class scientific and commercial expertise and infrastructure to lead the translation of massive amounts of genomic data into clinically-actionable results throughout the cancer patient’s journey, from screening and surveillance, to diagnosis, to treatment selection and monitoring. Genomic Health’s lead product, the Oncotype DX(R) breast cancer test, has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer and has been shown to predict the likelihood of recurrence in ductal carcinoma in situ (DCIS). In addition to this widely adopted test, Genomic Health provides the Oncotype DX colon cancer test, the first multi-gene expression test developed for the assessment of risk of recurrence in patients with stage II and stage III disease, and the Oncotype DXprostate cancer test, which predicts disease aggressiveness in men with low risk disease. As of June 30, 2013, more than 19,000 physicians in over 70 countries had ordered more than 375,000 Oncotype DX tests. The company is based in Redwood City, California with European headquarters inGeneva, Switzerland.

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