Modeling Minimal Residual Disease in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer deaths in the US. Patients with primary CRC will receive curative surgical resection, but up to 40% of patients will recur and develop metastatic disease after resection due to minimal residual disease. Minimal residual disease (MRD) results from cancer cells in the blood after resection. Unfortunately, MRD doesn't cause symptoms and isn't detectable by standard clinical tests such as CT scans. In our preliminary studies, we used a novel droplet-based microfluidics based technology to generate MicroOrganoSpheres (MOS) that can be used to grow cancer cells collected from portal venous blood during resection of the primary CRC. This has allowed us to isolate and characterize cancer cells representing MRD after resection of primary CRC. We now hypothesize that cancer cells that represent MRD that are resistant to standard of care therapy will lead to recurrence. In this grant, we propose to 1) Determine if cancer cells that are resistant to standard of care therapy are more likely to metastasize and lead to recurrence and 2) Perform high throughput drug screen on resistant clones to determine therapy that can prevent recurrence. The rationale for and impact of this study is that it will allow us identify and characterize cancer cells representing MRD after resection of a patient's primary CRC. The completion of this proposal will result in better understanding of tumor biology of MRD that determines recurrence and metastasis. This will lead to the development of clinical trials in the adjuvant setting to improve upon current adjuvant treatment after primary resection and ultimately, such findings will improve outcomes for patients with primary CRC by eradicating MRD leading to higher rates of cure after surgical resection Project Number: 1R21CA307993-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: SHIAOWEN HSU | Institution: DUKE UNIVERSITY, DURHAM, NC | Award Amount: $415,257 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 CTH-Z (56)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11278760