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International team created to improve detection of colorectal cancer

20 Nov 2014
International team created to improve detection of colorectal cancer

Stand Up To Cancer and the Dutch Cancer Society, Kankerbestrijding, along with the American Association for Cancer Research, SU2C’s Scientific Partner, announced the formation of an international Dream Team of top research scientists with the goal of improving early detection of colorectal cancer, currently the world’s fourth-leading cause of cancer death.

“Too many cases of colon cancer escape detection until the disease is in its advanced stages,” said Prof Arnold J. Levine, of the Institute for Advanced Study in Princeton, New Jersey, and the Rutgers Cancer Institute of New Jersey and co-chair of the selection committee.

“Better tests are needed to help detect colon cancer in its early stages when it can be more successfully treated.”

The project, entitled SU2C-KWF Molecular Early Detection of Colorectal Cancer, will be funded by a Stand Up To Cancer Dream Team Translational Cancer Research Grant for 6 million euros (approximately $7.6 million USD or £4.7 million GBP) over four years.

“This collaborative research works very well with the Dutch national colorectal population-screening programme, which will provide the Dream Team with 10,000 patients,” said Prof Hans Clevers at the Hubrecht Institute in Utrecht, the Netherlands, president of the Royal Netherlands Academy of Arts and Sciences, and a co-chair of the selection committee.

“Funding from the SU2C-KWF partnership can promote the development of new technologies in diagnostic and prognostic testing that will make real differences in patients’ lives.”

Prof Gerrit A. Meijer of pathology at VU University Medical Center in Amsterdam, will serve as leader of the SU2C-KWF Dream Team, with Prof Victor E. Velculescu, MD of oncology and pathology at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, serving as co-leader.

Meijer will continue as team leader after he moves to the Netherlands Cancer Institute in early 2015.

“We believe that we can reduce death from colorectal cancer by providing a more accurate screening test as well as a disease recurrence test that will be cost-effective and simple for the patient,” said Meijer.

“Much of the basic work has already been done, so we hope to move rapidly toward perfecting the tests and demonstrating their safety and effectiveness.”

The team will focus on validation of highly sensitive molecular tests that detect cancer-specific molecules, called biomarkers, in stool samples, indicating the presence of cancer or precancerous lesions in the colon or rectum.

The team will also develop a blood test that will fill a gap in treatment of early stage colorectal cancer by helping to identify patients who can benefit from chemotherapy after surgery.

“Our work will translate scientific breakthroughs on new ‘liquid biopsy’ technologies for noninvasive detection of cancer to improve outcomes for colorectal cancer patients,” Velculescu said.

“The international collaboration will take advantage of the best science on both sides of the Atlantic.”

The MEDOCC project is the third collaboration between SU2C and KWF.

Teams previously announced focused on the prospective use of DNA-guided personalised cancer treatment and use of tumour organoids – tiny living cell clusters – to study drug sensitivity. 

Colorectal cancer is the third most common cancer (after lung and breast), and the fourth leading cause of death from cancer (after lung, liver, and stomach), in the world, and is second only to lung cancer as a cause of cancer death in developed countries, according to the World Health Organisations' International Agency for Research on Cancer.

In the United States, for example, it is the second leading cancer killer of men and women combined.

Patients can be effectively treated when the tumour is detected and removed early; however, the disease often develops without symptoms until it has reached an advanced stage.

Screening is the most effective strategy for decreasing the rate at which colorectal cancer occurs and number of deaths it causes, with incidence and mortality rates declining in countries where screening has been introduced.

Stool or faecal based tests are widely used in Western Europe and Asia and increasingly in the US, with testing for blood (the faecal immunochemical test or FIT) as the standard approach.

Although FIT  has the potential to reduce colorectal cancer mortality by around 30 percent, improvements are needed urgently as approximately one-third of cancers, and more than two-thirds of pre-cancerous lesions, are missed by this test.

The sensitivity and accuracy of testing can be greatly improved using molecular stool tests, which detect cancer-specific biomarkers, such as DNA or proteins from cancer cells that are shed from the colon wall.

The US Food and Drug Administration recently approved the first stool-based colorectal screening test that detects blood and cancer-associated DNA changes and was better in clinical trial than FIT for detection of colorectal cancer.

The SU2C-KWF Dream Team’s goal is to move highly sensitive molecular testing for colorectal cancer to the next level so it can become available to patients in everyday life.

Their first aim is to improve molecular stool-based tests by using the best combination of cancer-associated DNA and/or protein biomarkers, so that these tests can go from the individual level to population screening.

This new test will be compared directly against the current test in 10,000 individuals participating in the Dutch national population-screening programme for colorectal cancer.

Their second aim will be to develop a molecular blood test for circulating cancer-associated DNA in order to improve identification of early stage colorectal cancer patients with a poor prognosis.

Patients in the early stage generally do not receive chemotherapy after surgery because 80 percent survive the disease.

The SU2C-KWF Dream Team hopes to develop a molecular blood test that identifies the other 20 percent of early stage colorectal cancer patients whose survival may be improved by chemotherapy after surgery.

The project is expected to start early in 2015, with development of the new test in the first two years and the screening trial in the third year.

Grant guidelines stipulated that the leader of the project must be from a research institute located in the Netherlands, while co-leaders can be from research institutes in any country.

Each project must include at least two research institutes located in the Netherlands and at least one research institute outside the Netherlands.

At least 50 percent of the grant funds must be allocated to research conducted in the Netherlands.

In addition to the team leaders, a multidisciplinary group of experts who make up the Dream Team as principals are: Manon van Engeland, programme leader in oncology at Maastricht University Medical Center; Prof Ernst J. Kuipers of gastroenterology at Erasmus University Medical Center in Rotterdam; Prof Evelien Dekker of gastrointestinal oncology at the Academic Medical Center of the University of Amsterdam; and Miriam Koopman, medical oncologist at the University Medical Center Utrecht.

Laypersons serving as patient advocates on the Dream Team are Marcia K. Horn, president and chief executive officer of the International Cancer Advocacy Network, and Jolien C.M. Pon, a colorectal cancer survivor and board member of the Foundation for Patients with Cancer in the Alimentary Canal and president of the SPKS colorectal cancer patient group.

Source: AARC