Discovery through clinical sequencing in oncology

Abstract

The molecular characterization of tumors now informs clinical cancer care for many patients. This advent of molecular oncology has been driven by the expanding number of therapeutic biomarkers that can predict sensitivity to both approved agents and investigational agents. Beyond its role in driving clinical-trial enrollments and guiding therapy in individual patients, large-scale clinical genomics in oncology also represents a rapidly expanding research resource for translational scientific discovery. Here we review the progress, opportunities, and challenges of scientific and translational discovery from prospective clinical genomic screening programs now routinely conducted for patients with cancer.

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Fig. 1: Balancing accessibility, utility, and discovery in clinical genomics.
Fig. 2: Facets of clinical sequencing that drive translational discovery science.
Fig. 3: The known unknowns and potential pitfalls of retrospective biomarker analyses.

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Acknowledgements

We thank M.F. Berger and D.B. Solit for discussions. This work was supported by US National Institutes of Health awards P30 CA008748, U54 OD020355 (B.S.T.), R01 CA207244 (D.M.H., B.S.T.), R01 CA204749 (B.S.T.), and R01 CA245069 (B.S.T.).

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Correspondence to Barry S. Taylor.

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D.M.H. reports receiving research funding from AstraZeneca, Puma Biotechnology, and Loxo Oncology, and personal fees from Atara Biotherapeutics, Chugai Pharma, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer, Debiopharm Group, and Genentech. B.S.T. reports receiving honoria and research funding from Genentech and Illumina and advisory board activities for Boehringer Ingelheim and Loxo Oncology, a wholly owned subsidiary of Eli Lilly.

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Donoghue, M.T.A., Schram, A.M., Hyman, D.M. et al. Discovery through clinical sequencing in oncology. Nat Cancer 1, 774–783 (2020). https://doi.org/10.1038/s43018-020-0100-0

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