A new chapter in targeting kinase enzymes in cancer

Nature作者:Alice T. Shaw2026年9月29日正文已收录本站
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Inhibitors of tyrosine kinase enzymes have been a cornerstone in precision cancer treatments. Now, targeted protein degraders could reshape therapeutic options.

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  1. Alice T. Shaw
    1. Alice T. Shaw is in the Department of Medical Oncology, Dana-Farber Cancer Institute and at Harvard Medical School, Boston, Massachusetts 02215, USA.

Targeted therapies have led to striking improvements in outcomes for people who have advanced cancer. Small molecules that inhibit the function of kinase enzymes that have acquired cancer-promoting activity have been particularly effective at treating lung cancer. Twenty-eight kinase inhibitors have been approved by the US Food and Drug Administration for nine molecular subsets of the disease. Although these inhibitors can result in cancer remission, in some cases lasting years, many people’s cancers eventually return. This is often because the kinase has acquired changes in amino-acid residues at or around the kinase’s active site, causing resistance to the drug. Writing in Nature, Conery et al.1 report an alternative and potentially powerful approach to treating these cancers that eliminates the target kinase rather than just inhibiting its function.

Nature 658, 41-43 (2026)

doi: https://doi.org/10.1038/d41586-026-02776-y

References

  1. Conery, A. R. et al. Nature 658, 241–249 (2026).

    Article  Google Scholar 

  2. Otano, I., Ucero, A. C., Zugazagoitia, J. & Paz-Ares, L. Nature Rev. Clin. Oncol. 20, 143–159 (2023).

    Article  PubMed  Google Scholar 

  3. Soda, M. et al. Nature 448, 561–566 (2007).

    Article  PubMed  Google Scholar 

  4. Kwak, E. L. et al. N. Engl. J. Med. 363, 1693–1703 (2010).

    Article  PubMed  Google Scholar 

  5. Schneider, J. L., Lin, J. J. & Shaw, A. T. Nature Cancer 4, 330–343 (2023).

    Article  PubMed  Google Scholar 

  6. Peters, S. et al. N. Engl. J. Med. 377, 829–838 (2017).

    Article  PubMed  Google Scholar 

  7. Shaw, A. T. et al. N. Engl. J. Med. 383, 2018–2029 (2020).

    Article  PubMed  Google Scholar 

  8. Johnson, T. W. et al. J. Med. Chem. 57, 4720–4744 (2014).

    Article  PubMed  Google Scholar 

  9. Lin, J. J. et al. Cancer Discov. 14, 2367–2386 (2024).

    Article  PubMed  Google Scholar 

  10. Yoda, S. et al. Cancer Discov. 8, 714–729 (2018).

    Article  PubMed  Google Scholar 

  11. Gillespie, C. S. et al. J. Thorac. Oncol. 18, 1703–1713 (2023).

    Article  PubMed  Google Scholar 

  12. Liu, D. et al. Ann. Oncol. 31, 1207–1215 (2020).

    Article  PubMed  Google Scholar 

  13. Dagogo-Jack, I. et al. Clin. Cancer Res. 26, 2535–2545 (2020).

    Article  PubMed  Google Scholar 

Download references

Competing Interests

A.T.S has consulted for or received honorariums from Triana Biomedicines, Pfizer, Nuvalent, Genetech/Roche and Astellas.

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