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Molecular Pharmacology

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OtherArticle

Novel human-derived RET fusion NSCLC cell lines have heterogeneous responses to RET inhibitors and differential regulation of downstream signaling

Laura Schubert, Anh T. Le, Adriana Estrada-Bernal, Andrea E. Doak, Minjae Yoo, Sarah E. Ferrara, Andrew Goodspeed, Fumi Kinose, Uwe Rix, Aik-Choon Tan and Robert C. Doebele
Molecular Pharmacology April 1, 2021, MOLPHARM-AR-2020-000207; DOI: https://doi.org/10.1124/molpharm.120.000207
Laura Schubert
1Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, United States of America
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Anh T. Le
1Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, United States of America
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Adriana Estrada-Bernal
1Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, United States of America
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Andrea E. Doak
1Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, United States of America
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Minjae Yoo
1Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, United States of America
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Sarah E. Ferrara
2University of Colorado Comprehensive Cancer Cenver, University of Colorado Anschutz Medical Campus, United States of America
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Andrew Goodspeed
3Department of Pharmacology, University of Colorado Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, United States of America
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Fumi Kinose
4Moffitt Cancer Center, United States of America
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Uwe Rix
4Moffitt Cancer Center, United States of America
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Aik-Choon Tan
5Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, United States of America
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Robert C. Doebele
1Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, United States of America
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  • For correspondence: robert.doebele@cuanschutz.edu

Data Supplement

  • Data Supplement -

    Supplemental Figure 1 - A. Representative phase contrast images from InCucyte of CUTO22, CUTO32, CUTO42 and LC-2/Ad cells under untreated conditions show different cellular morphologies.

    Supplemental Figure 2 - RET inhibitors rapidly decrease RET activation and is sustained for up to 24 hours.

    Supplemental Figure 3 - CUTO32 cells treated with indicated concentrations of ponatinib, RXDX-105 or BLU-667 for 2 hours.

    Supplemental Figure 4 - . CUTO32 cells are sensitive to PLK1 and Aurora kinase inhibitors in drug screen.

    Supplemental Figure 5 - Normalized expression in counts per million (CPM) of selected genes from RNA sequencing.

    Supplemental Figure 6 - Co-inhibition of MET does not sensitize RET+ cells to RET inhibitors.

    Supplemental Figure 7 - Average mouse weight measurements for xenograft experiments.

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