Article
MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistance.
Nature - 1 Feb 2026
White Mark, Mills Megan L, Millett Laura M, Gilroy Kathryn, Hong Yourae, Zeiger Lucas B, Simpson Rosalin J, Corry Shania M, Ligeza Amelia, Lannagan Tamsin R M, Susanti Susanti, Ridgway Rachel A, Yazgili Ayse S, Grzesiak Lucile, Amirkhah Raheleh, Ford Catriona A, Vlahov Nikola, Tovell Hannah, Officer-Jones Leah, Ficken Catherine, Pennie Rachel, Najumudeen Arafath K, Raven Alexander, Nasreddin Nadia, Chauhan Ekansh, Papanastasiou Andrew S, Nixon Colin, Morrison Vivienne, Jackstadt Rene, Graham Janet S, Miller Crispin J, Ross Sarah J, Barry Simon T, Pavet Valeria, Wilson Richard H, Le Quesne John, Dunne Philip D, Tejpar Sabine, Leedham Simon, Campbell Andrew D, Sansom Owen J
Abstract excerpt
The colorectal epithelium is rapidly renewing, with remarkable capacity to regenerate following injury. In colorectal cancer (CRC), this regenerative capacity can be co-opted to drive epithelial plasticity. Although oncogenic MAPK signalling in CRC is common, with frequent mutations of both KRAS (40-50%) and BRAF (10%)1, inhibition of this pathway typically drives resistance clinically. Here, given the...
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