Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentPreclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs
Colclough N, Chen K, Johnström P, Strittmatter N, Yan Y, Wrigley GL, Schou M, Goodwin R, Varnäs K, Adua SJ, Zhao M, Nguyen DX, Maglennon G, Barton P, Atkinson J, Zhang L, Janefeldt A, Wilson J, Smith A, Takano A, Arakawa R, Kondrashov M, Malmquist J, Revunov E, Vazquez-Romero A, Moein MM, Windhorst AD, Karp NA, Finlay MRV, Ward RA, Yates JWT, Smith PD, Farde L, Cheng Z, Cross DAE. Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs. Clinical Cancer Research 2021, 27: 189-201. PMID: 33028591, DOI: 10.1158/1078-0432.ccr-19-1871.Peer-Reviewed Original ResearchConceptsBlood-brain barrier permeabilityBrain metastasesBrain penetranceBarrier permeabilityEGFR tyrosine kinase inhibitorsT790M resistance mutationMetastatic brain diseaseSubclinical brain metastasesSelective EGFR tyrosine kinase inhibitorOngoing clinical evaluationM resistance mutationTyrosine kinase inhibitorsBBB penetranceBrain tumor growthClinical efficacyEGFR-TKIEGFR-TKIsBrain penetrationClinical evaluationPreclinical comparisonPreclinical modelsPreclinical studiesCynomolgus macaquesOsimertinibTumor growth