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Review
. 2016 Nov 18;1(5):e000094.
doi: 10.1136/esmoopen-2016-000094. eCollection 2016.

Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls

Peter Horak  1 , Stefan Fröhling  1 , Hanno Glimm  1
Affiliations
Review

Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls

Peter Horak et al. ESMO Open. .

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.

Keywords: Clinical Trial Design; Next-Generation Sequencing; Personalized Medicine; Precision Oncology; Whole-exome Sequencing.

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Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
DKTK MASTER is an example of whole-exome and transcriptome sequencing-based precision oncology programme. Following patient consent and study enrolment, biopsies are taken and processed in a certified laboratory using standardised protocols and storage methods. Pathological diagnosis and tumour cell content are validated by an independent pathologist. After DNA and RNA isolation and library preparation, NGS on an Illumina HiSeq 2500 platform is performed. Bioinformatical analysis is followed by data curation and validation of putative molecular targets. Following discussion in a molecular tumour board meeting, further enrolment in clinical trials and other personalised treatment strategies are recommended. CNV, copy number variant; FISH, fluorescence in situ hybridisation; NGS, next-generation sequencing; NCT IIT, National Center for Tumour Diseases investigator initiated trial; qRT-PCR, quantitative real-time polymerase chain reaction; SNV, single nucleotide variant.
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