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- W4382502030 endingPage "112696" @default.
- W4382502030 startingPage "112696" @default.
- W4382502030 abstract "Treatment options for patients with NRAS-mutant melanoma are limited and lack an efficient targeted drug combination that significantly increases overall and progression-free survival. In addition, targeted therapy success is hampered by the inevitable emergence of drug resistance. A thorough understanding of the molecular processes driving cancer cells’ escape mechanisms is crucial to tailor more efficient follow-up therapies. We performed single-cell RNA sequencing of NRAS-mutant melanoma treated with MEK1/2 plus CDK4/6 inhibitors to decipher transcriptional transitions during the development of drug resistance. Cell lines resuming full proliferation (FACs [fast-adapting cells]) and cells that became senescent (SACs [slow-adapting cells]) over prolonged treatment were identified. The early drug response was characterized by transitional states involving increased ion signaling, driven by upregulation of the ATP-gated ion channel P2RX7. P2RX7 activation was associated with improved therapy responses and, in combination with targeted drugs, could contribute to the delayed onset of acquired resistance in NRAS-mutant melanoma." @default.
- W4382502030 created "2023-06-30" @default.
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- W4382502030 date "2023-07-01" @default.
- W4382502030 modified "2023-10-16" @default.
- W4382502030 title "Single-cell transcriptomics of NRAS-mutated melanoma transitioning to drug resistance reveals P2RX7 as an indicator of early drug response" @default.
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- W4382502030 doi "https://doi.org/10.1016/j.celrep.2023.112696" @default.
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