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Functional precision cancer medicine—moving beyond pure genomics

Abstract

The essential job of precision medicine is to match the right drugs to the right patients. In cancer, precision medicine has been nearly synonymous with genomics. However, sobering recent studies have generally shown that most patients with cancer who receive genomic testing do not benefit from a genomic precision medicine strategy. Although some call the entire project of precision cancer medicine into question, I suggest instead that the tools employed must be broadened. Instead of relying exclusively on big data measurements of initial conditions, we should also acquire highly actionable functional information by perturbing—for example, with cancer therapies—viable primary tumor cells from patients with cancer.

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Figure 1

Debbie Maizels/Springer Nature

Figure 2: Dynamic BH3 profiling.

Debbie Maizels/Springer Nature

Figure 3: Multipronged precision medicine approach to rationally assembling combination regimens.

Debbie Maizels/Springer Nature

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Acknowledgements

I would like to acknowledge P. Bhola for assistance with Figure 1 and the entire Letai laboratory for conversations over years that have stimulated ideas contained in this article. I also gratefully acknowledge funding from National Institutes of Health grant R01CA205967.

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Correspondence to Anthony Letai.

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A.L. discloses consulting for AbbVie, Bayer, Astra Zeneca, XrX, Merrimack Pharmaceuticals, and Novartis; research sponsorship in his laboratory by AbbVie, AstraZeneca, XrX, and Novartis; inventorship on patents owned by Dana-Farber Cancer Institute regulating BH3 profiling and dynamic BH3 profiling; and being a cofounder and equity holder of Leap Oncology and Flash Therapeutics.

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Letai, A. Functional precision cancer medicine—moving beyond pure genomics. Nat Med 23, 1028–1035 (2017). https://doi.org/10.1038/nm.4389

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