Genomics-guided pre-clinical development of cancer therapies

Abstract

Since the approval of trastuzumab for the treatment of breast cancers more than two decades ago, many clinically effective targeted anti-cancer therapies have been developed. Here we consider the evidence that supports genomics-guided drug development and review the concept of oncogene addiction, including recent findings that inform this therapeutic approach. We consider non-oncogene addiction and how this synthetic-lethal paradigm could expand the range of new therapies, particularly for currently undruggable cancers. We discuss how CRISPR-based genetic screening is enhancing the ability to identify new targets. We conclude by considering opportunities for expanding the scope and refining the use of precision cancer medicines.

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Fig. 1: Targeting oncogene addiction and non-oncogene addiction in cancer.
Fig. 2: A genomics-guided precision medicine knowledge bank to guide therapy.

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Acknowledgements

We thank the Garnett laboratory and A. Bassett for suggestions. M.J.G.’s laboratory is supported by the Wellcome Trust (206194), SU2C (SU2CAACR-DT1213), The British Lung Foundation, Cancer Research UK (C44943/A22536) and Open Targets.

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Correspondence to Mathew J. Garnett.

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U.M. is an employee of AstraZeneca, and M.J.G. received research funding from AstraZeneca.

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Francies, H.E., McDermott, U. & Garnett, M.J. Genomics-guided pre-clinical development of cancer therapies. Nat Cancer 1, 482–492 (2020). https://doi.org/10.1038/s43018-020-0067-x

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