Fig. 4: Afatinib inhibits EGFR R252C-driven tumor cell proliferation and tumor growth in vivo.
From: An alternative EGFR activation by patient-derived R252C mutation promotes cancer progression
a, b U87, U251, and H1299 cells with or without EGFR R252C mutation were treated with either vehicle (DMSO) or 1 μM afatinib. Cell proliferation assay (a, b) and colony formation assay (c) were performed in these cells. Relative cell proliferation of U87, U251, and H1299 cells was normalized to the day 1 value (a). The inhibition ratio of cell proliferation by afatinib was calculated at day 7 (b). d Luciferase-expressing U87 cells with or without EGFR R252C were intracranially injected into randomized athymic nude mice (five mice per group). After 35 days, afatinib was administered via oral gavage (10 mg/kg body weight) for a duration of 14 days. Bioluminescence imaging of mice was carried out to examine tumor growth. Data represent the mean ± s.d. of five mice. e Luciferase-expressing H1299 cells with or without EGFR R252C were injected into the left lung of randomized athymic nude mice (five mice per group). After 21 days, afatinib was administered via oral gavage (10 mg/kg body weight) for a duration of 14 days. Bioluminescence imaging of mice was carried out to examine tumor growth. Data represent the mean ± s.d. of five mice. f Chest CT and brain MRI images of a patient with multifocal lung cancer harboring EGFR R252C mutation, before and after treatment with afatinib. g Intact treatment timeline of the patient harboring EGFR R252C mutation. a,c Data represent the mean ± s.d. of three biologically independent experiments. a, c, d, e. Unpaired, two-tailed t-test.
