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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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.
U.M. is an employee of AstraZeneca, and M.J.G. received research funding from AstraZeneca.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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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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