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. 2020 Jan 3;11:74. doi: 10.1038/s41467-019-13771-5

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a–c Evaluation of xenografts treated with VER and/or ALC. Tumor lysates were immunoblotted with the indicated antibody. The experimental protocol is shown in (a). Increased expression of Mcl-1 and Bcl-xL in xenografts after ALC treatment (b). The increased expression of the two proteins were canceled and apoptosis activity was increased when the xenografts were treated with ALC + VER (c). d–e Combinatorial therapy with VER and ALC provided a longer tumor remission in ALK-rearranged xenografts on nude mice. Tumor volume curve (d) and tumor volumes on day 50 (e) in 34 xenografts generated from H2228, an ALC-sensitive cell line. Vehicle and VER monotherapy groups were subjected to observations for 28 days only to avoid unnecessary pain. Significance was evaluated using unpaired t-test. f–g A tracer experiment using KTOR1 xenografts on NSG mice. Tumor volume curve (f) and tumor volumes on day 36 (g) in 35 xenografts. Significance was evaluated using unpaired t-test. h–i Combinatorial therapy with VER and ALC provided enhanced tumor control in ALC-resistant ALK-rearranged xenografts on nude mice. Tumor volume curve (h) and tumor volumes on day 35 (i) in 25 xenografts generated from H2228-ARY, an ALC-resistant cell line with YAP1 dependency. Vehicle and VER monotherapy groups were subjected to observations for 18 days only to avoid unnecessary pain. Significance was evaluated using unpaired t-test. VER verteporfin, ALC alectinib. Error bars indicate ± S.D. *P < 0.05.