SBIR Phase I: Accelerating Targeted Therapies for Colitis-Associated Cancer Using Patient-Derived Human Tissue Models

The broader/commercial impact of this Small Business Innovation Research (SBIR) Phase I project is to improve how inflammation-associated cancers are studied and treated by enabling more accurate, human-relevant preclinical models. Patients with chronic inflammatory diseases such as ulcerative colitis and Crohn’s disease face an elevated risk of developing colorectal cancer, yet current models do not capture the full complexity of these conditions. This project will support the development of patient-derived tissue systems that better represent human disease, reduce reliance on animal models, and improve the predictability of drug development. The expected outcomes will accelerate the identification of effective therapies, reduce the cost and time of clinical development, and support national priorities for advancing non-animal testing approaches. The project will also contribute to workforce development through training in advanced tissue engineering and translational research and broaden access to technologies that support more precise cancer treatment. The proposed project will develop patient-derived, multicellular tissue models to study colitis-associated cancer, a form of colorectal cancer driven by chronic inflammation. Existing preclinical systems are either oversimplified, relying on single cell types, or use co-culture approaches that do not self-assemble into tissue-like structures with integrated epithelial, stromal, and immune interactions, limiting their predictive value. The project will generate patient-derived, multicellular tissue models that self-assemble to integrate epithelial, stromal, and immune compartments and reproduce inflammation-driven tumor initiation and early progression. Research objectives include establishing reproducible models spanning normal, inflammatory, and dysplastic states; validating disease-relevant structural and molecular features using histological and biomarker analyses; and evaluating therapeutic responses using standard and targeted agents. The anticipated outcome is a scalable and reproducible system capable of capturing patient-specific disease biology and enabling quantitative assessment of treatment response. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.