Circulating tumor DNA (ctDNA) are tiny fragments of DNA shed by cancer cells that can be detected in the blood of cancer patients. Detection of ctDNA after completion of all curative intent therapies in the absence of any cancer on scans (i.e. minimal residual disease, MRD) is associated with a very high risk of recurrence. Thus, ctDNA is a very good marker for stratifying risk of recurrence and holds great promise in radically changing our approach to taking care of CRC patients. However, since only small amounts ctDNA are present after surgery, more sensitive assays for MRD are needed. Furthermore, whether patients whose ctDNA disappears with chemotherapy have improved survival is unknown...

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Circulating tumor DNA (ctDNA) are tiny fragments of DNA shed by cancer cells that can be detected in the blood of cancer patients. Detection of ctDNA after completion of all curative intent therapies in the absence of any cancer on scans (i.e. minimal residual disease, MRD) is associated with a very high risk of recurrence. Thus, ctDNA is a very good marker for stratifying risk of recurrence and holds great promise in radically changing our approach to taking care of CRC patients. However, since only small amounts ctDNA are present after surgery, more sensitive assays for MRD are needed. Furthermore, whether patients whose ctDNA disappears with chemotherapy have improved survival is unknown. Conversely, whether administering additional therapies to patients who are MRD positive after all planned therapies and before overt evidence of cancer will improve outcomes is unkown. To address these deficiencies, we propose to further refine a ctDNA (CRC23) assay specific for CRC developed by our group with a goal to significantly improve detection of MRD. Simultaneously, our group will lead a large trial of over 1,000 CRC patients undergoing curative therapies from institutions in Texas and / or the MD Anderson Cancer Network to collect serial blood and tumor samples. At the end of the study period, these samples will be analyzed with the improved CRC23 assay to validate its performance. In a pilot trial at our institution, patients who are MRD positive are being treated with a novel drug that works by enhancing the immune system’s ability to eliminate small cancer deposits. We propose to conduct additional experiments in blood and tissue samples from these patients to understand better the activity of this drug.

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