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- W4385402452 abstract "Evidence is mounting for cross-resistance between immune checkpoint and targeted kinase inhibitor therapies in cutaneous melanoma patients. Since the loss of the transcription factor, SOX10, causes tolerance to MAPK pathway inhibitors, we used bioinformatic techniques to determine if reduced SOX10 expression/activity is associated with immune checkpoint inhibitor resistance. We integrated SOX10 ChIP-seq, knockout RNA-seq, and knockdown ATAC-seq data from melanoma cell models to develop a robust SOX10 gene signature. We used computational methods to validate this signature as a measure of SOX10-dependent activity in independent single-cell and bulk RNA-seq SOX10 knockdown, cell line panel, and MAPK inhibitor drug-resistant datasets. Evaluation of patient single-cell RNA-seq data revealed lower levels of SOX10-dependent transcripts in immune checkpoint inhibitor-resistant tumors. Our results suggest that SOX10-deficient melanoma cells are associated with cross-resistance between targeted and immune checkpoint inhibitors and highlight the need to identify therapeutic strategies that target this subpopulation." @default.
- W4385402452 created "2023-07-31" @default.
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- W4385402452 creator A5085398803 @default.
- W4385402452 date "2023-09-01" @default.
- W4385402452 modified "2023-10-12" @default.
- W4385402452 title "Gene Signature Reveals Decreased SOX10-Dependent Transcripts in Malignant Cells from Immune Checkpoint Inhibitor-Resistant Cutaneous Melanoma Tumors" @default.
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- W4385402452 doi "https://doi.org/10.1016/j.isci.2023.107472" @default.
- W4385402452 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37636077" @default.
- W4385402452 hasPublicationYear "2023" @default.
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