Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220795887> ?p ?o ?g. }
- W4220795887 abstract "Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells." @default.
- W4220795887 created "2022-04-03" @default.
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- W4220795887 date "2022-03-16" @default.
- W4220795887 modified "2023-10-18" @default.
- W4220795887 title "Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma" @default.
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- W4220795887 doi "https://doi.org/10.1038/s41467-022-28801-y" @default.
- W4220795887 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35296667" @default.
- W4220795887 hasPublicationYear "2022" @default.