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Primary liver cancer genome sequencing: translational implications and challenges

Demosthenes E Ziogas1,2, Ioannis D Kyrochristos1,3, Georgios K Glantzounis3

  • 1a Centre for Biosystems and Genome Network Medicine , Ioannina University , Ioannina , Greece.

Expert Review of Gastroenterology & Hepatology
|July 18, 2017
PubMed
Abstract

Insights

Next-generation sequencing (NGS) can improve understanding of primary liver cancer (PLC) molecular pathways and heterogeneity. Integrating NGS into clinical trials is crucial for developing targeted therapies and identifying new drug targets for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

Area of Science:

  • Genomics and Molecular Oncology
  • Translational Cancer Research

Background:

  • Primary liver cancer (PLC) has a poor prognosis due to limited understanding of molecular drivers, therapeutic resistance, and relapse.
  • Current treatments like surgical resection, sorafenib, and regorafenib offer limited survival benefits for advanced PLC.

Purpose of the Study:

  • To critically review next-generation sequencing (NGS) applications in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) for clinical implications.
  • To propose strategies for integrating NGS into clinical trials for improved understanding and targeted therapy development.

Main Methods:

  • Comprehensive review of existing next-generation sequencing (NGS) studies, including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing (RNAseq).
  • Critical analysis of challenges in identifying clinically actionable genomic alterations (GAs) from NGS data.

Main Results:

  • NGS application on clinical samples can elucidate tumorigenesis, genetic/genomic heterogeneity, and aid in molecular classification for targeted therapies.
  • Challenges exist in translating NGS findings into clinically significant outcomes.

Conclusions:

  • Recommendations for valid identification of clinically crucial genomic alterations (GAs) by NGS are proposed.
  • Integration of NGS into well-designed clinical trials is essential for advancing PLC treatment.
  • Detection of genomic heterogeneity via NGS can facilitate trials for prognostic/predictive biomarkers and novel oncotarget discovery.
Keywords:
Next-generation sequencingWESWGScancer genomedrugshepatocellular cancerintrahepatic cholangiocarcinomanovel oncotargetsumbrella and basket studies

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