A Novel mTORC1/2 Inhibitor (MTI-31) Inhibits Tumor Growth, Epithelial-Mesenchymal Transition, Metastases, and Improves Antitumor Immunity in Preclinical Models of Lung Cancer

A Novel mTORC1/2 Inhibitor (MTI-31) Inhibits Tumor Growth, Epithelial-Mesenchymal Transition, Metastases, and Improves Antitumor Immunity in Preclinical Models of Lung Cancer

We aimed to investigate efficacy and mechanism of MTI-31 (LXI-15029), a novel mTORC1/mTORC2 inhibitor currently in human trial (NCT03125746), in non-small cell lung cancer (NSCLC) models of multiple driver mutations and tyrosine kinase inhibitor (TKI)-resistance. Gene depletion, inhibitor treatment,...

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Veröffentlicht in:Clinical cancer research 2019-06, Vol.25 (12), p.3630-3642
Hauptverfasser: Zhang, Qianwen, Zhang, Yan, Chen, Yaqing, Qian, Jianchang, Zhang, Xuesai, Yu, Ker
Format: Artikel
Sprache:eng
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Zusammenfassung:We aimed to investigate efficacy and mechanism of MTI-31 (LXI-15029), a novel mTORC1/mTORC2 inhibitor currently in human trial (NCT03125746), in non-small cell lung cancer (NSCLC) models of multiple driver mutations and tyrosine kinase inhibitor (TKI)-resistance. Gene depletion, inhibitor treatment, immunological, flow cytometry, cellular, and animal studies were performed to determine and efficacy in NSCLC models of driver mutations and elucidate roles by mTOR complexes in regulating migration, epithelial-mesenchymal transition (EMT), metastasis, intracranial tumor growth, and immune-escape. MTI-31 potently inhibited cell proliferation (IC
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-18-2548