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Cancer dependencies

Hyperactivation of oncogenic driver pathways as a precision therapeutic strategy

Nature Genetics volume 55, pages 1613–1614 (2023)Cite this article

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Many precision cancer therapies function by inhibiting oncogenic signaling pathways. A new study describes the counterintuitive finding that forced hyperactivation of the same pathways can also enable selective tumor targeting.

Several oncogene-targeted therapies exist, including inhibitors of well-established disease drivers such as BCR-ABL, EGFR, ALK and BRAF. In many cases, these agents have transformed disease management and substantially extended patients’ lives. However, targeted therapies have well-known limitations. For example, in some cases, key nodes in oncogenic driver pathways have proven difficult to drug. Furthermore, even when potent and selective targeted therapies are developed, their application can be limited by challenges such as on-target, off-tissue toxicities2 and the eventual development of resistance3.

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Fig. 1: Schematic depicting the relationship between oncogenic pathway activity and cellular fitness.

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  1. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA

    Kris C. Wood

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  1. Kris C. Wood
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Correspondence to Kris C. Wood.

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The author declares no competing financial interest.

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Wood, K.C. Hyperactivation of oncogenic driver pathways as a precision therapeutic strategy. Nat Genet 55, 1613–1614 (2023). https://doi.org/10.1038/s41588-023-01493-w

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