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Program Official
Principal Investigator
Robert E. Schoen
Awardee Organization

University Of Pittsburgh At Pittsburgh
United States

Fiscal Year
2024
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Blood-Based Testing for Advanced Adenoma

The goal of our Clinical Validation Center (CVC) is to advance and validate blood-based detection of colorectal advanced adenoma. Whereas blood-based testing for invasive colorectal cancer is progressing, with multiple companies pursuing products, the ability of blood-based testing to detect advanced adenomas, the premalignant lesions closest to invasive cancer, is uncertain. To optimally impact colorectal cancer incidence, blood-based biomarkers cannot just detect cancer, they should also have sufficient sensitivity to identify subjects with advanced adenomas. For our CVC, we organized and assembled a network of highly skilled clinical centers including a focus on minority populations, to prospectively collect well-characterized, highquality blood specimens from a large number of subjects with advanced adenoma prior to undergoing polypectomy and serially post-polypectomy. From the same clinical centers, we will collect blood specimens from control subjects. Specimens will be collected and processed using standard protocols, and relevant demographic and clinical variables will be captured to facilitate biomarker validation studies. Specifically, we will use these well-characterized specimens to validate our data on the utility of original, innovative techniques for molecular detection of advanced adenomas including RealSeqS in combination with custom machine learning algorithms such as SignaL. We propose two Specific Aims. In Specific Aim 1, we will conduct a phase 2 case-control study to validate our novel methods for advanced adenoma detection. We will prospectively recruit patients with advanced adenoma (N=400) and site-specific control subjects (N=400) for comparison to the case subjects. In Specific Aim 2, we will utilize serial blood specimens systematically collected postpolypectomy from our case subjects to determine whether our novel molecular detection techniques can be used to predict likelihood of recurrence and potentially guide surveillance colonoscopy exams. Advanced adenomas are the important, next frontier in non-invasive colorectal cancer screening, and our CVC is equipped to profoundly advance blood-based detection of advanced adenoma.

Publications

  • Douville C, Lahouel K, Kuo A, Grant H, Avigdor BE, Curtis SD, Summers M, Cohen JD, Wang Y, Mattox A, Dudley J, Dobbyn L, Popoli M, Ptak J, Nehme N, Silliman N, Blair C, Romans K, Thoburn C, Gizzi J, Schoen RE, Tie J, Gibbs P, Ho-Pham LT, Tran BNH, Tran TS, Nguyen TV, Goggins M, Wolfgang CL, Wang TL, Shih IM, Lennon AM, Hruban RH, Bettegowda C, Kinzler KW, Papadopoulos N, Vogelstein B, Tomasetti C. Machine learning to detect the SINEs of cancer. Science translational medicine. 2024 Jan 24;16(731):eadi3883. Epub 2024 Jan 24. PMID: 38266106
  • Lahouel K, Douville C, Diergaarde B, Cohen JD, Grant H, Kuo A, Ansari SK, Wang Y, O'Broin-Lennon AM, Popoli M, Ptak J, Silliman N, Dobbyn L, Nehme N, Tie J, Gibbs P, Papadopoulos N, Kinzler KW, Vogelstein B, Schoen RE, Tomasetti C. A Blood-Based Assay for Detection of Patients with Advanced Adenomas. Cancer research communications. 2025 Apr 1;5(4):621-631. PMID: 40099973
  • Ladabaum U, Mannalithara A, Weng Y, Schoen RE, Dominitz JA, Desai M, Lieberman D. Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology. 2024 Jul;167(2):378-391. Epub 2024 Mar 26. PMID: 38552670
  • Ladabaum U, Mannalithara A, Schoen RE, Dominitz JA, Lieberman D. Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Annals of internal medicine. 2024 Dec;177(12):1610-1620. Epub 2024 Oct 29. PMID: 39467291
  • Diergaarde B, Young G, Hall DW, Mazloom A, Costa GL, Subramaniam S, Palomares MR, Garces J, Baehner FL, Schoen RE, Exact Sciences MRD Group, Basu G, Bungo J, Flake D, Hu J, Hunicke-Smith S, Johnson A, LoBello J, Lockton S, Marti T, Melanson S, Song B, Wallace M, Wojcik M, You M, You J. Circulating Tumor DNA as a Marker of Recurrence Risk in Stage III Colorectal Cancer: The α-CORRECT Study. Journal of surgical oncology. 2025 Jul;132(1):175-186. Epub 2025 Jan 25. PMID: 39865324
  • Shaukat A, Burke CA, Chan AT, Grady WM, Gupta S, Katona BW, Ladabaum U, Liang PS, Liu JJ, Putcha G, Robertson DJ, Schoen RE, Meng Z, Piscitello A, Sun CK, Xu C, Lin CJ, Lee LC, Baldo L, Levin TR, PREEMPT CRC Investigators. Clinical Validation of a Circulating Tumor DNA-Based Blood Test to Screen for Colorectal Cancer. JAMA. 2025 Jul 1;334(1):56-63. PMID: 40455622