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Novel Preclinical Patient-Derived Lung Cancer Models Reveal Inhibition of HER3 and MTOR Signaling as Therapeutic Strategies for NRG1 Fusion-Positive Cancers by Igor Odintsov; Marissa S. Mattar; Allan J.W. Lui; Michael Offin; Christopher Kurzatkowski; Lukas Delasos; Inna Khodos; Marina Asher; Robert M. Daly; Natasha Rekhtman; Elisa de Stanchina; Gopinath Ganji; Marc Ladanyi; Romel Somwar is a Medicine article available to read on EtoBox.
What is Novel Preclinical Patient-Derived Lung Cancer Models Reveal Inhibition of HER3 and MTOR Signaling as Therapeutic Strategies for NRG1 Fusion-Positive Cancers about?
## Introduction: Nrg1 rearrangements produce chimeric ligands that subvert the erbb pathway to drive tumorigenesis. a better understanding of the signaling networks that mediate transformation by nrg1 fusions is needed to inform effective therapeutic strategies. unfortunately, this has been hampered by a paucity of patient-derived disease models that faithfully recapitulate this molecularly defined cancer subset. ## Methods: Patient-derived xenograft (pdx) and cell line models were established from nrg1-rearranged lung adenocarcinoma samples. transcriptomic, proteomic, and biochemical analyses were performed to identify activated pathways. efficacy studies were conducted to evaluate her3- and mtor-directed therapies. ## Results: We established a pair of pdx and cell line models of invasive mucinous lung adenocarcinoma (luad) (luad-0061as3, slc3a2-nrg1), representing the first reported paired in vitro and in vivo model of nrg1-driven tumors. growth of luad-0061as3 models was reduced by the anti-her3 antibody gsk2849330. transcriptomic profiling revealed activation of the mtor pathway in lung tumor samples with nrg1 fusions. phosphorylation of several mtor effectors (s6 and 4ebp1) wa
Who reads Novel Preclinical Patient-Derived Lung Cancer Models Reveal Inhibition of HER3 and MTOR Signaling as Therapeutic Strategies for NRG1 Fusion-Positive Cancers?
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- Author
- Igor Odintsov; Marissa S. Mattar; Allan J.W. Lui; Michael Offin; Christopher Kurzatkowski; Lukas Delasos; Inna Khodos; Marina Asher; Robert M. Daly; Natasha Rekhtman; Elisa de Stanchina; Gopinath Ganji; Marc Ladanyi; Romel Somwar
- Publisher
- Elsevier BV
- Published
- 2021
- Language
- EN
- Field
- Medicine (Health Sciences)