Establishment of novel cholangiocarcinoma cell lines with ARID1A deficiency and preclinical validation of synthetic lethality therapies.

ABSTRACT: Cholangiocarcinoma (CCA) is a highly lethal malignancy with poor prognosis due to its resistance to conventional chemotherapy and limited number of targetable mutations. The recurrent loss-of-function mutation of the tumor suppressor ARID1A represents a key vulnerability potentially exploitable via synthetic lethality. To advance research in this area, we successfully established and characterized two novel CCA cell lines, SiSP-K01 and SiSP-K05, derived from moderately differentiated intrahepatic CCA. Both models were confirmed to carry ARID1A heterozygous loss and complete protein depletion, authentically reproducing the target genotype. Comprehensive molecular and phenotypic profiling (including karyotype, growth kinetics, 100% in vivo tumorigenesis, and tumor marker expression) confirme

SUBMITTER: Prasopporn S 

PROVIDER: S-EPMC12627850 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature