Abstract
Primary liver cancers, including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is an important cause of cancer-related deaths in Thailand and worldwide due to ineffectiveness of current available treatments. The recently developed organoid technology, which allows long-term culture of patient-derived liver cancer cells in 3D while maintaining morphology, expression pattern, and the genetic heterogeneity of the original tumors, has been shown to be powerful research tool for the discovery of biomarkers and therapeutic drugs for various cancers. In this study we successfully established 31 cancer organoids line from Thai patients with CCA and HCC, and characterized in detail these organoids with whole exome sequencing, whole transcriptomics study, single-cell RNA sequencing and pharmacophenotyping with various anticancer drugs. Our data shows patient specific response in CCA organoids and supports the usage of personalized treatment strategy for CCA. Moreover, we identified new potential biomarkers and novel compounds that can be applied to CCA management. One of the candidates for CCA drugs showed promising result in 3/3 PDX models tested. For HCC, although there is high heterogeneity among patients’ sample and limited drug response to standard drugs used in HCC management, we identified new subpopulation of HCC with high stemness, unique immunogenic profiles, and treatment response which may become interesting candidate for developing new treatment option for HCC. Overall, we successfully generate database and important tools for future development of new treatment for Thai patient with liver cancer.
