Review Article | Published:

The emerging clinical relevance of genomics in cancer medicine

Nature Reviews Clinical Oncologyvolume 15pages353365 (2018) | Download Citation

Abstract

The combination of next-generation sequencing and advanced computational data analysis approaches has revolutionized our understanding of the genomic underpinnings of cancer development and progression. The coincident development of targeted small molecule and antibody-based therapies that target a cancer’s genomic dependencies has fuelled the transition of genomic assays into clinical use in patients with cancer. Beyond the identification of individual targetable alterations, genomic methods can gauge mutational load, which might predict a therapeutic response to immune-checkpoint inhibitors or identify cancer-specific proteins that inform the design of personalized anticancer vaccines. Emerging clinical applications of cancer genomics include monitoring treatment responses and characterizing mechanisms of resistance. The increasing relevance of genomics to clinical cancer care also highlights several considerable challenges, including the need to promote equal access to genomic testing.

Key points

  • Genomic assays that enable the characterization of the somatic and germline defects in individual tumour samples are increasingly being used in clinical diagnostics as a means of identifying therapeutic options.

  • Many technical and cost-associated considerations have a role in decision-making processes regarding the implementation of cancer genomics assays into clinical practice.

  • Genomic methods can reveal individual targetable alterations, mutational load, complex mutation signatures, and tumour-specific antigens, which might inform the utilization of targeted therapies, immune-checkpoint inhibitors, and personalized anticancer vaccines.

  • The occurrence of shared targetable alterations across diverse tumour types has prompted new paradigms in the application of genomic profiling and the design of clinical trials.

  • These assays increasingly provide information that is pertinent to clinical cancer care, although several important attendant challenges surround their implementation.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

AACR Project GENIE: http://www.aacr.org/Research/Research/Pages/aacr-project-genie.aspx#.Wi5Vi1WnGUk

IEDB Analysis Resource, Epitope Prediction and Analysis Tools: http://tools.immuneepitope.org/main/

NCI-MATCH Trial (Molecular Analysis for Therapy Choice): https://www.cancer.gov/about-cancer/treatment/clinical-trials/nci-supported/nci-match

NIH Genomic Data Commons: https://gdc.cancer.gov

The Global Alliance for Genomics and Health: https://www.ga4gh.org/

The Novartis Signature trial programme: http://www.trials.novartis.com/en/clinical-trials/us-oncology/oncology/signature/about/

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Affiliations

  1. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Michael F. Berger
  2. Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    • Elaine R. Mardis
  3. Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH, USA

    • Elaine R. Mardis

Authors

  1. Search for Michael F. Berger in:

  2. Search for Elaine R. Mardis in:

Contributions

Both authors made a substantial contribution to all aspects of the preparation of this manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Elaine R. Mardis.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/s41571-018-0002-6

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