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. 2022 Dec 7;13:7551. doi: 10.1038/s41467-022-35134-3

Fig. 7. Epithelial TGFβ/ALK5 signalling exposes therapeutic vulnerability to MAPK-targeted therapies.

Fig. 7

a Survival plot for VilCreER;Apcfl/+;KrasG12D/+;Alk5CA mice treated daily with vehicle or vandetanib/ZD6474 and aged until clinical endpoint following tamoxifen induction. n = 6 mice per group. P = 0.02, log-rank test. b Representative CD31 and p-ERK staining on small intestinal tumour tissue from mice described in a. Scale bar, 100 μm. c Small intestinal (SI) tumour number (left) and burden (right) per mouse from mice described in a. n = 5 vehicle (pink), n = 6 ZD6474 (aqua) mice. Data were ±s.e.m; P = 0.98 (tumour number), *P = 0.02 (tumour burden). Two-tail Mann–Whitney U-test. d Survival plot for VilCreER;Apcfl/+;KrasG12D/+;Alk5CA mice treated daily with MEK1/2 inhibitor (MEKi) or EGFR inhibitor (EGFRi) and aged until clinical endpoint following tamoxifen induction. n = 24 untreated (grey), n = 14 MEKi (red), n = 10 EGFRi (blue) mice. P = 1.0 × 10−4 (MEKi), P = 3.0 × 10−2 (EGFRi), log-rank test. e Representative H&E staining of small intestinal tissue from VilCreER;Apcfl/+;KrasG12D/+;Alk5CA mice following indicated treatments. The bottom panels are a magnification of the boxed areas in the corresponding top panels. Scale bar, 100 μm. f Total tumour number (left) and burden (right) per mouse from mice described in d. n = 15 untreated (grey), n = 8 MEKi (red), n = 13 EGFRi mice (blue). Data were ±s.e.m; Tumour number: P = 0.09 (MEKi), **P = 0.005 (EGFRi), Tumour burden: *P = 0.01 (MEKi), *P = 0.03 (EGFRi). Two-tail Mann–Whitney U-test.