In vitro modeling of hepatocellular carcinoma molecular subtypes for anti-cancer drug assessment
| Autor: | Tizita Z. Zeleke, Hadassa Hirschfield, Venugopalan D. Nair, C Billie Bian, Yujin Hoshida, Takaaki Higashi, Shigeki Nakagawa, Bryan C. Fuchs |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Somatic cell Clinical Biochemistry Antineoplastic Agents Biology Biochemistry Transcriptome 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Gene expression Biomarkers Tumor medicine Carcinoma Humans Molecular Targeted Therapy Epigenetics Molecular Biology beta Catenin Gene Expression Profiling Liver Neoplasms Azepines Triazoles medicine.disease 3. Good health Bromodomain 030104 developmental biology Drug development 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Molecular Medicine Original Article alpha-Fetoproteins Drug Screening Assays Antitumor |
| Zdroj: | Experimental & Molecular Medicine |
| ISSN: | 2092-6413 1226-3613 |
| DOI: | 10.1038/emm.2017.164 |
| Popis: | Tractable experimental model that accounts for inter-tumor molecular heterogeneity is a key element of anti-cancer drug development. Hepatocellular carcinoma is known to exhibit highly heterogeneous molecular aberrations across the tumors, including somatic genetic and epigenetic alterations. Previous studies showed that molecular tumor subtypes determined by transcriptome, as a comprehensive functional readout, are reproducibly observed across global patient populations irrespective of geographic and etiological variations. Here we demonstrate that transcriptomic hepatocellular carcinoma subtypes, S1 and S2, determined by our previous transcriptome meta-analysis of multiple clinical hepatocellular carcinoma cohorts, are presented in a panel of hepatoma cell lines widely used by the research community. Interestingly, cell line that resembles gene expression pattern of S3 subtype, representing less aggressive tumors, was not identified in the panel. MYC pathway-activated S2-like cell lines showed higher sensitivity to a small molecule BET bromodomain inhibitor, (+)-JQ1, which has anti-MYC activity. These results support the use of hepatoma cell lines as models to evaluate molecular subtype-specific drug response, which is expected to lead to development of tailored, precision care of the patients with hepatocellular carcinoma. |
| Databáze: | OpenAIRE |
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