MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression

Autor: Anne E. Willis, Laura McDonald, George Skalka, Andrew D. Campbell, Heather McKinnon, Kevin M. Haigis, John R. P. Knight, Sebastian May-Wilson, Kathryn Gilroy, William J. Faller, Emma Stanway, Leah Officer, Rachael C. L. Smith, Joshua D.G. Leach, Joseph A. Waldron, Rachel A. Ridgway, Nicola Valeri, Ewan M. Smith, Arafath Kaja Najumudeen, Nahum Sonenberg, Joanne Edwards, Rene Jackstadt, Ana Teodósio, John Le Quesne, Dustin J. Flanagan, Anne Cheasty, Georgios Kanellos, Kerri McArthur, Christopher G. Proud, Constantinos Alexandrou, Georgios Vlachogiannis, Neil P. Jones, Nikola Vlahov, Owen J. Sansom, Kathryn Af Pennel, Craig MacKay, Martin E. Swarbrick, Martin Bushell

Publikováno v: Knight, J R P, Alexandrou, C, Skalka, G L, Vlahov, N, Pennel, K, Officer, L, Teodosio, A, Kanellos, G, Gay, D M, May-Wilson, S, Smith, E M, Najumudeen, A K, Gilroy, K, Ridgway, R A, Flanagan, D J, Smith, R C L, McDonald, L, MacKay, C, Cheasty, A, McArthur, K, Stanway, E, Leach, J D, Jackstadt, R, Waldron, J A, Campbell, A D, Vlachogiannis, G, Valeri, N, Haigis, K M, Sonenberg, N, Proud, C G, Jones, N P, Swarbrick, M E, McKinnon, H J, Faller, W J, Quesne, J L, Edwards, J, Willis, A E, Bushell, M & Sansom, O J 2021, ' MNK Inhibition Sensitizes KRAS-Mutant Colorectal Cancer to mTORC1 Inhibition by Reducing eIF4E Phosphorylation and c-MYC Expression ', Cancer discovery, vol. 11, no. 5, pp. 1228-1247 . https://doi.org/10.1158/2159-8290.CD-20-0652

KRAS-mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, are significantly less potent in KRAS-mutant colorectal cancer. Using Kras-

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https://doi.org/10.1158/2159-8290.CD-20-0652