Precision medicine for hepatocelluar carcinoma using molecular pattern diagnostics: results from a preclinical pilot study

Rahul Agarwal, Yuan Cao, Klaus Hoffmeier, Nicolas Krezdorn, Lukas Jost, Alejandro Rodriguez Meisel, Ruth Jüngling, Francesco Dituri, Serena Mancarella, Björn Rotter, Peter Winter, Gianluigi Giannelli

Research output: Contribution to journalArticle

Abstract

The aim of this study was to design a road map for personalizing cancer therapy in hepatocellular carcinoma (HCC) by using molecular pattern diagnostics. As an exploratory study, we investigated molecular patterns of tissues of two tumors from individual HCC patients, which in previous experiments had shown contrasting reactions to the phase 2 transforming growth factor beta receptor 1 inhibitor galunisertib. Cancer-driving molecular patterns encompass - inter alias - altered transcription profiles and somatic mutations in coding regions differentiating tumors from their respective peritumoral tissues and from each other. Massive analysis of cDNA ends and all-exome sequencing demonstrate a highly divergent transcriptional and mutational landscape, respectively, for the two tumors, that offers potential explanations for the tumors contrasting responses to galunisertib. Molecular pattern diagnostics (MPDs) suggest alternative, individual-tumor-specific therapies, which in both cases deviate from the standard sorafenib treatment and from each other. Suggested personalized therapies use kinase inhibitors and immune-focused drugs as well as low-toxicity natural compounds identified using an advanced bioinformatics routine included in the MPD protocol. The MPD pipeline we describe here for the prediction of suitable drugs for treatment of two contrasting HCCs may serve as a blueprint for the design of therapies for various types of cancer.

Original languageEnglish
Pages (from-to)e2867
JournalCell Death and Disease
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 8 2017

Keywords

  • Journal Article

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    Agarwal, R., Cao, Y., Hoffmeier, K., Krezdorn, N., Jost, L., Meisel, A. R., Jüngling, R., Dituri, F., Mancarella, S., Rotter, B., Winter, P., & Giannelli, G. (2017). Precision medicine for hepatocelluar carcinoma using molecular pattern diagnostics: results from a preclinical pilot study. Cell Death and Disease, 8(6), e2867. https://doi.org/10.1038/cddis.2017.229