A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer
Yochum Z, Cades J, Mazzacurati L, Neumann N, Khetarpal S, Chatterjee S, Wang H, Attar M, Huang E, Chatley S, Nugent K, Somasundaram A, Engh J, Ewald A, Cho Y, Rudin C, Tran P, Burns T. A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer. Molecular Cancer Research 2017, 15: 1764-1776. PMID: 28851812, PMCID: PMC5712248, DOI: 10.1158/1541-7786.mcr-17-0298.Peer-Reviewed Original ResearchConceptsOncogene-driven NSCLCTwist1 functionPatient-derived xenograft mouse modelsMarked anti-tumor activityEpithelial-mesenchymal transition transcription factorsNon-small cell lung cancer tumorigenesisSolid tumor malignanciesSingle-cell disseminationLung cancer tumorigenesisNovel therapeutic strategiesXenograft mouse modelCell lung cancer tumorigenesisEffects of harmineAnti-tumor activityConnectivity mapping analysisE2A proteinsNSCLC cellsNSCLC tumorigenesisMutant NSCLCAnalogs/derivativesMouse modelTherapeutic strategiesHarmine treatmentDimer partnerTherapeutic targetTWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer
Kumar V, Yochum Z, Devadassan P, Huang E, Miller E, Baruwal R, Rumde P, GaitherDavis A, Stabile L, Burns T. TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer. Oncogene 2024, 43: 1431-1444. PMID: 38485737, PMCID: PMC11068584, DOI: 10.1038/s41388-024-02987-5.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsTKI resistanceMET amplificationEpithelial-mesenchymal transitionMET tyrosine kinase inhibitorsOvercome resistanceTyrosine kinase inhibitor resistanceTargetable oncogenic driversResistance in vitroEffective therapeutic strategySuppression of p27Inhibition of Twist1MET alterationsPDX modelsMET pathwayHGF/MET pathwayOncogenic driversLung cancerLung tumorigenesisKinase inhibitorsP27 expressionTherapeutic strategiesPharmacological inhibitionDownstream mediatorTwist1