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Plasticity as Resistance: KRAS Inhibition Reveals WNT Adaptation in Metastatic Colorectal Cancer
George Eng1,2, Omer H Yilmaz1,2
1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
None:
Centonze and colleagues demonstrate that KRASG12D inhibition in metastatic colorectal cancer triggers rapid transcriptional reprogramming from a metastasis-associated EMP1+ state to a WNT-driven LGR5+ stem cell-like state, a plastic adaptation captured through real-time live cell imaging, revealing cell state conversion as a mechanism of therapeutic resistance that can be exploited through combinatorial targeting. See related article by Centonze et al., p. 320.
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