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Precision medicine for cancer with next-generation functional diagnostics

Nature Reviews Cancer volume 15, pages 747–756 (2015)Cite this article

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Abstract

Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies. Recently, several 'next-generation' functional diagnostic technologies have been reported, including novel methods for tumour manipulation, molecularly precise assays of tumour responses and device-based in situ approaches; these address the limitations of the older generation of chemosensitivity tests. The promise of these new technologies suggests a future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients.

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Figure 1: Next-generation approaches for cancer precision medicine.
Figure 2: Dynamic BH3 profiling can predict patient responses to cancer therapies.

Change history

  • 10 November 2015

    The sentence in Box 1 referring to non-synonymous mutations should have referred to synonymous mutations. This has been corrected to state "Even synonymous mutations can have effects on cellular fitness100."

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Acknowledgements

The authors apologize to investigators whose research they were unable to include owing to space considerations.

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Authors and Affiliations

  1. Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, Boston, 02114, Massachusetts, USA

    Adam A. Friedman, David E. Fisher & Keith T. Flaherty

  2. Dermatology and Cutaneous Biology Research Center, Massachusetts General Hospital, 149 East 13th Street, Charlestown, 02129, Massachusetts, USA

    David E. Fisher

  3. Dana-Farber Cancer Institute, Harvard Medical School, 440 Brookline Avenue, Mayer 430, Boston, 02215, Massachusetts, USA

    Anthony Letai

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Correspondence to Adam A. Friedman.

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Competing interests

A.L. is a co-inventor on patents related to BH3 profiling for the selection of therapies for patients with cancer. A.A.F., A.L., D.E.F. and K.T.F. hold equity in and serve on the Scientific Advisory Board of Leap Oncology.

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Friedman, A., Letai, A., Fisher, D. et al. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer 15, 747–756 (2015). https://doi.org/10.1038/nrc4015

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