Figure 2.

Current disease models for studying ICC. (A) ICC cancer cell lines. There are many cell lines established from primary tumor cells. Three representative cell lines are listed. HuCCA-1 was derived from a Thai patient with liver fluke infection. MT-CHCO1 and KKU-213L5 were both established from patient-derived xenografts (PDX). (B) 3D patient-derived tissue-like organoids. Organoids preserve the properties of primary tumor cells as well as tissue heterogeneity. (C) Genetically engineered mouse model (GEMM). A GEMM of ICC was generated by inducing oncogenic KRAS mutation and homozygous PTEN deletion in mouse liver. (D) Orthotopic patient-derived xenograft (PDX). In orthotopic PDX mouse models, patient-derived tumor cells are transplanted into the same organ from which the patient's cancer originated, followed by stabilizing the tumors in the animals. (E) A mouse model of ICC created by CRISPR/Cas9 gene editing. CRISPR/Cas9 is used to introduce mutations to the selected tumor suppressor genes including Arid1a, Trp53, Tet2, Pten, Cdkn2a, Apc, Brca1/2, and Smad4, which lead to ICC in the gene-edited mice.