Molecular heterogeneity in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous primary liver cancer, and currently there exist only a few options of targeted therapy. Histopathologically, iCCA is sub-classified according to morphology (mass forming type, periductal infiltrating type, and intraductal growing type) and histology (small duct type and large duct type). According to different histopathological types, clinical features such as risk factors and prognosis vary. Recent developments in genomic profiling have revealed several molecular markers for poor prognosis and activation of oncogenic pathways. Exploration of molecular characteristics of iCCA in each patient is a major challenge in a clinical setting, and there is no effective molecular-based targeted therapy. However, several recent studies suggested molecular-based subtypes with corresponding clinical and pathological features. Even though the subtypes have not yet been validated, it is possible that molecular features can be predicted based on clinicopathological characteristics and that this could be used for a more rational approach to integrative clinical and molecular subclassification and targeted therapy. In this review, we explored the genomic landscape of iCCA and attempted to find relevance between clinicopathologic and molecular features in molecular subtypes in several published studies. The results reveal future directions that may lead to a rational approach to the targeted therapy.