Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases

TLDR

Chemotherapy improves survival, yet heterogeneity in tumor chemosensitivity leads to unnecessary treatment and toxicity, and tumor organoids offer an individualized platform to address this issue. The study aims to develop a platform that preemptively identifies patients who will benefit from treatment by establishing organoid cultures from metastatic biopsies. Organoid cultures were established from metastatic biopsy specimens with high success and maintained genetic fidelity to the original metastasis. The data support translating this technology into clinical use as an ex vivo screening platform to tailor treatment.

Abstract

Significance Chemotherapy has been proven in clinical studies to improve overall survival significantly. Unfortunately, there is a significant degree of heterogeneity in tumor chemosensitivity, often resulting in unnecessary treatment and needless exposure to toxic side-effects. A platform is needed that can identify preemptively which patients will or will not benefit from treatment. Tumor organoids, 3D cultures of cancer cells, present such an individualized platform. In this study we demonstrate that organoid cultures can be established from metastatic biopsy specimens with a high success rate and genetically represent the metastasis they were derived from. These data support the translation of this innovative technology to the clinic as an ex vivo screening platform for tailoring treatment.