Abstract A018: Investigating the role of cancer-associated fibroblasts in colorectal cancer peritoneal metastasis

Abstract Colorectal cancer (CRC) is the third most common cancer type worldwide. Besides the lung and liver, the peritoneum, a serous membrane lining the abdominal cavity, is one of the most common sites of CRC metastasis. Notably, the presence of peritoneal metastases (PMs) is associated with poor survival, as their presence reflects advanced disease and the efficacy of current therapies in these lesions is limited. Recent studies found that the CRC peritoneal metastatic disease is associated with a stroma-rich phenotype, suggesting an important role of cancer-associated fibroblasts (CAFs) in supporting CRC PM. However, current models of CRC PM using murine CRC cell lines failed to recapitulate this phenotype. Therefore, we employed the recently developed AKPS CRC organoid model, which contains four common mutations (APC-null, Tp53-null, Smad4-null, and KRAS-G12D) observed in human CRC patients, and established CRC peritoneal metastasis by intraperitoneal delivery of AKPS tumor cells into immunocompetent mice. The AKPS-derived PM tumors contain a large amount of stroma and resemble the histopathological features of human CRC PM. Utilizing this model, we will examine the tumor microenvironment (TME) of AKPS PM via single-cell and spatial transcriptomics profiling and compare it with the TME of both the primary tumor and liver metastasis. Ultimately, the goal of this study is to better understand the unique roles of CAFs in CRC PM and to identify potential therapeutic targets for treating this disease. Citation Format: Qihao Ren, Nathaniel West, Louis Vermeulen. Investigating the role of cancer-associated fibroblasts in colorectal cancer peritoneal metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr A018.