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SU2C-Dutch Cancer Society Translational Cancer Research Dream Team Progress Update

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Stand Up To Cancer-Dutch Cancer Society Translational Cancer Research Dream Team Progress Report

Molecular Early Detection of Colorectal Cancer (MEDOCC)

Funding: €6,000,000

Leader: Gerrit A. Meijer, MD, PhD, Netherlands Cancer Institute (NKI)
Co-Leader: Victor E. Velculescu, MD, PhD, Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center


Fast Facts on Colorectal Cancer:

  • In the United States, colorectal cancer is the third most commonly diagnosed cancer and the third leading cause of cancer-related deaths in men and women.
  • Colorectal cancer rates are highest in African American men and women and lowest in Asian/Pacific Islander men and women.

Fast Facts on Prevention Tips:

  • Screening is key to colorectal cancer prevention and is recommended for men and women beginning at age 50.
  • Adopt a physically active lifestyle, and maintain a healthy weight throughout life.
  • Consume a healthy diet with an emphasis on plant sources. Limit your consumption of processed and red meats, as well as alcoholic beverages.

 

Project Background:


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

Patients can be effectively treated when the tumor 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 fecal based tests are widely used in Western Europe and Asia and increasingly in the U.S., with testing for blood (the fecal 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 that detect cancer-specific biomarkers, such as DNA or proteins from cancer cells that are shed from the colon wall. The U.S. 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-DCS 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 program 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-DCS 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.

Status Updates:

6 months
In the first 6 months of funding the Dream Team has established their working groups and developed strategies, including regular monthly web-conferences, to successfully collaborate across institutions in the Netherlands and the United States. They report progress as follows:

  • They are making progress in modifying methods to analyze blood plasma DNA for use in fecal samples
  • They had made progress in identifying cancer-associated proteins that are more sensitive than current tests for detection of colorectal cancer and can therefore be used to improve the stool-based screening test
  • They have made progress in establishing the DNA sequencing analysis methods that they will use in cancer tissue as well as blood samples in early stage colorectal cancer

In the next 6 months the Dream Team will continue optimizing the biomarkers that they will use for screening and residual colorectal cancer detection.

12 months
In the second 6 months of funding the Dream Team reports progress on both Specific Aims.

Aim 1:

  • The Dream Team reports some challenges in optimizing laboratory procedures to isolate DNA from stool.  They are working to overcome those difficulties.
  • They have identified a list of 10 promising DNA methylation biomarkers that they hope will provide them with a sensitive method to detect colorectal cancer in stool samples.
  • They continue to optimize laboratory approaches to measure colorectal cancer-associated proteins in stool.

Aim 2:

  • The Dream Team reports approval of an amendment to the Dutch trial, the Prospective Dutch Colorectal Cancer Cohort Study (PLCRC), which will allow them to move forward with testing how well liquid biopsies can identify stage II colorectal cancer patients who are high risk of disease recurrence after surgery.
  • They continue to adapt the approaches they developed in other cancers to liquid biopsy for colorectal cancer in blood samples. In the next 6 months the Dream Team plans to advance optimization of stool and blood tests for molecular detection of colorectal cancer. They will initiate the observational MEDOCC study in UMC Utrecht and other PLCRC participating hospitals throughout The Netherlands.

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