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The emerging clinical relevance of genomics in cancer medicine

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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Fig. 1: Clinical utility of genomic assays in cancer care.
Fig. 2: Clinical trial designs invoking cancer genomics assays.
Fig. 3: NGS-based neoantigen discovery.
Fig. 4: Liquid biopsy assays enable the monitoring of genomic alterations present in circulating tumour DNA.

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

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Correspondence to Elaine R. Mardis.

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Related links

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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Berger, M.F., Mardis, E.R. The emerging clinical relevance of genomics in cancer medicine. Nat Rev Clin Oncol 15, 353–365 (2018). https://doi.org/10.1038/s41571-018-0002-6

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