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KRAS degradation averts PDAC chemoresistance

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Effectively targeting deregulated KRAS signaling remains an unmet clinical need, as current approaches commonly lead to the development of chemoresistance in clinical settings. ADAM9-mediated lysosomal KRAS degradation is now shown to counteract PDAC chemoresistance independently of mutational status.

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Fig. 1: Targeting KRAS signaling in PDAC.

References

  1. Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. CA Cancer J. Clin. 73, 17–48 (2023).

    Article  PubMed  Google Scholar 

  2. Waters, A. M. & Der, C. J. Cold Spring Harb. Perspect. Med. 8, a031435 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Punekar, S. R., Velcheti, V., Neel, B. G. & Wong, K.-K. Nat. Rev. Clin. Oncol. 19, 637–655 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Huang, Y.-K. et al. Nat. Cancer https://doi.org/10.1038/s43018-023-00720-x (2024).

    Article  PubMed  Google Scholar 

  5. Skoulidis, F. et al. New Engl. J. Med. 384, 2371–2381 (2021).

    Article  CAS  PubMed  Google Scholar 

  6. Jänne, P. A. et al. New Engl. J. Med. 387, 120–131 (2022).

    Article  PubMed  Google Scholar 

  7. Zhao, Y. et al. Nature 599, 679–683 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  8. Awad, M. M. et al. New Engl. J. Med. 384, 2382–2393 (2021).

    Article  CAS  PubMed  Google Scholar 

  9. Bond, M. J., Chu, L., Nalawansha, D. A., Li, K. & Crews, C. M. ACS Cent. Sci. 6, 1367–1375 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Miyamoto-Sato, E. et al. Molecules 28, 5600 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shin, W. et al. Exp. Mol. Med. 50, 1–10 (2018).

    PubMed  PubMed Central  Google Scholar 

  12. Yamamoto, K. et al. J. Gastroenterol. 57, 603–618 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hosein, A. N., Dougan, S. K., Aguirre, A. J. & Maitra, A. Nat. Cancer 3, 272–286 (2022).

    Article  PubMed  Google Scholar 

  14. Rojas, L. A. et al. Nature 618, 144–150 (2023).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Petroni, G., Buqué, A., Zitvogel, L., Kroemer, G. & Galluzzi, L. Cancer Cell 39, 310–345 (2021).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. TUM School of Medicine and Health, Technical University Munich, Munich, Germany

    Laura Leonhardt & Matthias Hebrok

  2. Center for Organoid Systems, Technical University Munich, Garching, Germany

    Laura Leonhardt & Matthias Hebrok

  3. Institute for Diabetes and Organoid Technology, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany

    Laura Leonhardt & Matthias Hebrok

  4. Munich Institute of Biomedical Engineering (MIBE), Technical University Munich, Munich, Germany

    Matthias Hebrok

  5. German Center for Diabetes Research (DZD), Neuherberg, Germany

    Matthias Hebrok

  6. Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Matthias Hebrok

Authors
  1. Laura Leonhardt
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  2. Matthias Hebrok
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Corresponding author

Correspondence to Matthias Hebrok.

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Competing interests

M.H. holds stocks in Encellin Inc. and Thymmune Therapeutics Inc., consults for CV Next and holds stocks in the company, and is the co-founder of Minutia Inc. and holds stocks and options in the company. L.L. declares no competing interests.

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Leonhardt, L., Hebrok, M. KRAS degradation averts PDAC chemoresistance. Nat Cancer 5, 375–377 (2024). https://doi.org/10.1038/s43018-023-00708-7

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  • DOI: https://doi.org/10.1038/s43018-023-00708-7

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