Abstract 5158: Establishing novel patient-derived xenograft models for peritoneal metastasis in a racially diverse population

Abstract

Colorectal cancer (CRC) is highly treatable when localized, but survival drops sharply with metastasis, especially to the peritoneum (PM). CRC PM is particularly resistant to chemotherapy, emphasizing the need for models that replicate disease biology for use in drug discovery. Our study establishes reproducible CRC PM patient-derived xenografts (PDX) from a racially diverse patient population. Patients with CRC PM were recruited for a tissue collection study at a single academic tertiary care center. Tumor samples were collected under sterile conditions and prepared for subcutaneous propagation into NOD.Cg-Prkdcscid/J (NSG) mice. Next, tumor was harvested and reimplanted intraperitoneally into new NSG models. Peritoneal metastasis was induced via 1) Intraperitoneal injection of a single cell suspension or 2) Intraperitoneal tumor implantation via laparotomy. Post-necropsy, peritoneal carcinomatous index (PCI) was calculated and pictures were taken using a cross-polarization technique to allow for PCI scoring by an independent investigator. Collected tumor was processed for histological analysis. We developed four successful intraperitoneal PDX models using CRC PM derived from a 62-year-old non-Hispanic Black female with KRAS G12V mutation and a 60-year-old non-Hispanic White female with KRAS wildtype. Both tumors had microsatellite stability (MSS). All four PDX were representative of the human clinical condition as diffuse peritoneal metastases were found in each. The laparotomy group exhibited a higher tumor burden and PCI compared to the tumor injection group. In histological comparison of PDX to patient tissue, we observed that tumor gland formation and architecture were maintained. Early findings show that CRC PM PDX models can be successfully established from a racially diverse patient population. Intraperitoneal tumor implantation into NSG mice via laparotomy resulted in a higher PCI compared to tumor injection, though the latter may be more reproducible. Cross-polarization imaging optimized tumor visualization and allowed PCI scoring by an independent investigator. These models mimic gross and histologic characteristics of the original patient tumor. Future directions include extensive multi-omic profiling to further characterize each PDX. We aim to expand our PDX library to better represent CRC PM heterogeneity with a focus towards drug development. Citation Format: Vashti Bandy, Adam Khader, Praveen Bhoopathi, Vignesh Vudatha, Arunima Punjala, Jose Trevino, Bhaumik Patel, Leopoldo Fernandez, Savannah Gregg. Establishing novel patient-derived xenograft models for peritoneal metastasis in a racially diverse population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1): nr 5158.