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Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls
  1. Peter Horak,
  2. Stefan Fröhling,
  3. Hanno Glimm
  1. Department of Translational Oncology, National Center for Tumor Diseases Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany
  1. Correspondence to Dr Peter Horak; peter.horak{at}nct-heidelberg.de

Abstract

We live in an era of genomic medicine. The past five years brought about many significant achievements in the field of cancer genetics, driven by rapidly evolving technologies and plummeting costs of next-generation sequencing (NGS). The official completion of the Cancer Genome Project in 2014 led many to envision the clinical implementation of cancer genomic data as the next logical step in cancer therapy. Stemming from this vision, the term ‘precision oncology’ was coined to illustrate the novelty of this individualised approach. The basic assumption of precision oncology is that molecular markers detected by NGS will predict response to targeted therapies independently from tumour histology. However, along with a ubiquitous availability of NGS, the complexity and heterogeneity at the individual patient level had to be acknowledged. Not only does the latter present challenges to clinical decision-making based on sequencing data, it is also an obstacle to the rational design of clinical trials. Novel tissue-agnostic trial designs were quickly developed to overcome these challenges. Results from some of these trials have recently demonstrated the feasibility and efficacy of this approach. On the other hand, there is an increasing amount of whole-exome and whole-genome NGS data which allows us to assess ever smaller differences between individual patients with cancer. In this review, we highlight different tumour sequencing strategies currently used for precision oncology, describe their individual strengths and weaknesses, and emphasise their feasibility in different clinical settings. Further, we evaluate the possibility of NGS implementation in current and future clinical trials, and point to the significance of NGS for translational research.

  • Next-Generation Sequencing
  • Precision Oncology
  • Whole-exome Sequencing
  • Clinical Trial Design
  • Personalized Medicine

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors PH designed, wrote and reviewed the manuscript. SF and HG designed, commented and reviewed the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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