Reducing Colorectal Cancer Mortality with CF10
Abstract
Our project will develop a more effective treatment for advanced and metastatic colorectal cancer (mCRC), a Fiscal Year 2020 Peer Reviewed Cancer Research Program Topic Area. CRC is one of the most common malignancies diagnosed among active-duty military personnel and it is the third-leading cause of cancer mortality in the general population. Fluoropyrimidine drugs (FPs) such as 5-fluorouracil (5-FU) are widely used to treat CRC. While FPs provide a therapeutic benefit, these drugs are not very effective toward mCRC, and treatment is toxic to some patients. The lack of an effective treatment for mCRC affects mission readiness, and a new therapy that improves survival for patients with mCRC and is well tolerated would have a major impact. Our work focuses on developing polymers of the active form of FP drugs. We have shown that this approach improves anti-tumor activity and reduces damage to normal tissue. We recently demonstrated that our second-generation FP polymer CF10 localized to colon tumors and improved survival while causing less toxicity than 5- FU. CF10 also displayed promising anti-metastatic activity. Based upon these promising preliminary studies, we propose to undertake studies in rodent models of CRC metastasis that will provide definitive information on the superiority of CF10 relative to 5-FU. We will use a rat model to test if CF10 attacks liver metastases in a new way that involves initial uptake by liver cells. We will also test human CRC specimens for ability to metastasize in animal models and test whether CF10 is more effective than 5-FU at inhibiting metastatic progression. Finally, we will test if CF10 kills CRC cells in a way that causes the immune system to attack other CRC cells. Completing these studies will provide definitive data that could prove CF10 is superior to 5-FU for treating mCRC, inhibiting metastatic progression, and stimulating an anti-tumor immune response. The data generated in these studies will provide the basis for initiating clinical studies with CF10 within 3 years. The immediate target population would be patients with mCRC for whom current treatment is largely ineffective. CF10 could also benefit patients with earlier stage CRC by reducing risk for disease recurrence with decreased risk for serious morbidities due to treatment. Since CRC is one of the most commonly diagnosed malignancies among active-duty military personnel, Veterans, and the general population, our work will have a broad impact.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110575
Entities
People
- William Gmeiner
Organizations
- United States Army
- Wake Forest University