Targeting oncogenic KRAS holds great promise but is often limited by rapid adaptive resistance. A study now shows that RASH3D19 is regulated by microRNAs and promotes resistance to RAS inhibition by enhancing EGFR dimerization. Targeting RASH3D19 improves sensitivity to RAS inhibitors in preclinical settings.
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References
Przybyszewski, O. et al. Biomedicines 12, 1713 (2024).
Tsunoda, T. et al. Anticancer Res 31, 2453–2459 (2011).
Treekitkarnmongkol, W. et al. Nat. Cell Biol. https://doi.org/10.1038/s41556-025-01816-5 (2025).
Cox, A. D. & Der, C. J. Genes Dev. 39, 132–162 (2025).
Singhal, A., Li, B. T. & O’Reilly, E. M. Nat. Med. 30, 969–983 (2024).
Jänne, P. A. et al. N. Engl. J. Med. 387, 120–131 (2022).
de Langen, A. J. et al. Lancet 401, 733–746 (2023).
Ryan, M. B. et al. Cell Rep. 39, 110993 (2022).
Amodio, V. et al. Cancer Discov. 10, 1129–1139 (2020).
Szczepanek, J., Skorupa, M. & Tretyn, A. Cells 11, 1008 (2022).
Croce, C. M. Nat. Rev. Genet. 10, 704–714 (2009).
Tanaka, M. et al. J. Biol. Chem. 279, 41950–41959 (2004).
Yam, J. W., Jin, D. Y., So, C. W. & Chan, L. C. Blood 103, 1445–1453 (2004).
Fakih, M. G. et al. N. Engl. J. Med. 389, 2125–2139 (2023).
Srivastava, R. M. et al. Cancer Immunol. Res. 3, 936–945 (2015).
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Torphy, R.J., Pylayeva-Gupta, Y. Deciphering KRAS inhibitor resistance. Nat Cell Biol 28, 8–10 (2026). https://doi.org/10.1038/s41556-025-01757-z
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DOI: https://doi.org/10.1038/s41556-025-01757-z
