FIGURE 3

FIGURE 3

TNO155 sensitizes ALK-mutant zebrafish xenografts to ALK inhibitors. Zebrafish embryos (2 dpf) were injected with GFP-expressing Kelly (A), SH-SY5Y (B), or LAN-6 (C) cells costained with DiI dye. At 1 day post injection (1 DPI), xenografted larvae were submersed in TNO155, ceritinib, or lorlatinib alone or in combination treatments and incubated at 35°C for 72 hours. Tumor mass was assessed after 72 hours of drug exposure (4 DPI), and GFP fluorescence (area × pixel intensity) was quantified and normalized to pretreatment (1 DPI). Tumor cell invasion within the yolk-sac was visualized (A and D) and quantified (E) in Kelly larval xenografts treated with TNO155, ceritinib or lorlatinib alone or in combination for 72 hours. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant.