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Scottish Scientist Receives $208K to Use Proteomics Tools in Colon Cancer Study

A University of Aberdeen researcher has received £105,000 [$208,000] to identify proteins for early-stage colon cancer diagnosis.
Pathology professor Graeme Murray will use the funding, from the Association for International Cancer Research, to detect and identify biomarkers for the cancer.
Murray said he expects to begin his work in early May, which will use mass spectrometry-based methods. The funding, spread over two years, will be used partly to hire a postdoc to help with the work.
Murray told ProteoMonitor that his research will follow a “classic” proteomics approach and will use tumor samples collected from about 10 patients from the Aberdeen Royal Infirmary. Proteins will be separated by 2D gel electrophoresis, and proteins of interest will undergo peptide mass mapping by mass spectrometry. For validation, Murray will use immunohistochemistry and tissue microrarrays.
For the validation part of the research, Murray said he will expand to “several hundred” the number of samples.
The strongpoint of his research is access to the tumor samples from the hospital, which is a regional cancer center. Each year, the facility sees between 300 and 400 colon cancer patients, Murray said.
The work being funded by AICR is built on earlier research by Murray to identify biomarkers for advanced cases of colon cancer. Much of that work has focused on cytochromes P450 and matrix metalloproteinases. In 2006, he and collaborators published a paper in The Journal of Pathology that showed that chaperonin containing t-complex polypeptide 1 beta and TCP1 epsilon are overexpressed in colorectal adenocarcinomas, indicating they play a role in colorectal cancer.
As a pathologist, Murray said he leaves the bulk of the proteomics work to others — in the case of the AICR-funded research, the postdoc. But he said he has had “a long-standing interest in biomarkers, and in particular protein-based biomarkers,” spurred by a former postdoc in his lab who became involved in developing the core mass-spectrometry facility at the university.

“Hopefully, we can identify some markers that can aid in the identification of those patients who will progress. That will ultimately allow [for] therapeutic intervention.”

Each year, around 35,000 new cases of colon cancer are diagnosed in the UK. As with any cancer, the goal with colon cancer is to try to catch it in its early stages when the chances for survival can be optimized.
In Scotland in particular there is an acute need to find better diagnostics for the disease, according to the AICR: With 3,500 new diagnoses annually, Scotland has the highest rate of colon cancer in the UK, according to the association.
In the US, the National Cancer Institute anticipates 108,000 new cases of colon cancer this year, and nearly 50,000 deaths from colon and rectal cancer combined.
As Murray begins the AICR project, he said the goal is simple: to deliver more aggressive treatments to those patients who need them.
“The issue with early-stage disease is there’s a proportion of patients with early-stage disease [that] will progress and a proportion [that] will not progress,” Murray said. “Hopefully, we can identify some markers that can aid in the identification of those patients who will progress. That will ultimately allow [for] therapeutic intervention.”
Symptoms for the disease include abdominal pain, diarrhea, constipation, fecal occult blood, and bowel obstruction. In some instances, a patient may show no symptoms.
Several methods are currently used to screen for the cancer, including fecal occult blood tests; sigmoid- and colonoscopy, in which a lighted tube is inserted into the rectum and colon to check for polyps; and double-contrast barium enema, in which X-rays are taken of the colon and rectum for polyps, tumors, and lesions.
However, even with improvements in diagnostic methods, the outlook for many patients remains grim with a 50-percent five-year mortality rate, according to an AICR official.
“Although the outlook for patients with this type of cancer has improved significantly over the last 20 years, currently only about half of patients survive five years after diagnosis,” said Mark Matfield, the association’s scientific adviser, in a statement.
Recognizing the need and commercial opportunity for better diagnostics, several companies have developed or are trying to develop tests for the disease.
For instance, late last year Panacea Pharmaceutical launched its CC Detect serum-based test, available through its Panacea Laboratories [See PM 11/15/07]. The test measures the levels of human aspartyl (asparaginyl) beta-hydroxylase.
Also last year, Proteome Sciences entered into a collaboration with Onconome to characterize prostate and colon cancer antibodies developed by that company.
And in February 2007 Oxford Genome Sciences announced it had received a new round of equity investment to continue developing new colon cancer diagnostics and therapies [See PM 02/08/07].

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