دورية أكاديمية
Single-cell transcriptomics of NRAS-mutated melanoma transitioning to drug resistance reveals P2RX7 as an indicator of early drug response.
| العنوان: | Single-cell transcriptomics of NRAS-mutated melanoma transitioning to drug resistance reveals P2RX7 as an indicator of early drug response. |
|---|---|
| المؤلفون: | RANDIC, Tijana, MAGNI, Stefano, PHILIPPIDOU, Demetra, Margue, Christiane, GRZYB, Kamil, PREIS, Jasmin Renate, WROBLEWSKA, Joanna Patrycja, NAZAROV, Petr, MITTELBRONN, Michel, FRAUENKNECHT, Katrin, SKUPIN, Alexander, KREIS, Stephanie |
| المصدر: | Cell Reports, 42 (7), 112696 (2023-07-25) |
| بيانات النشر: | Elsevier B.V. |
| سنة النشر: | 2023 |
| المجموعة: | University of Luxembourg: ORBilu - Open Repository and Bibliography |
| مصطلحات موضوعية: | CP: Cancer, MEK/CDK4/6 co-inhibition, NRAS-mutant melanoma, P2RX7, drug resistance, single-cell RNA-sequencing, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, P2RX7 protein, human, Receptors, Purinergic P2X7, NRAS protein, Membrane Proteins, GTP Phosphohydrolases, Humans, Protein Kinase Inhibitors/pharmacology, Neoplasm/genetics, Cell Line, Tumor, Mutation/genetics, Proto-Oncogene Proteins B-raf/genetics, Purinergic P2X7/metabolism, Membrane Proteins/metabolism, GTP Phosphohydrolases/genetics, GTP Phosphohydrolases/metabolism, Transcriptome, Melanoma/drug therapy, Melanoma/genetics, Melanoma/metabolism |
| الوصف: | peer reviewed ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2211-1247 |
| العلاقة: | https://api.elsevier.com/content/article/PII:S2211124723007076?httpAccept=text/xmlTest; urn:issn:2211-1247; https://orbilu.uni.lu/handle/10993/58082Test; info:hdl:10993/58082; https://orbilu.uni.lu/bitstream/10993/58082/1/Randic%20et%20al%2c%202023.pdfTest; scopus-id:2-s2.0-85163502753; info:pmid:37379213; wos:001030571600001 |
| DOI: | 10.1016/j.celrep.2023.112696 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2023.112696Test https://orbilu.uni.lu/handle/10993/58082Test https://orbilu.uni.lu/bitstream/10993/58082/1/Randic%20et%20al%2c%202023.pdfTest |
| حقوق: | open access ; http://purl.org/coar/access_right/c_abf2Test ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7AC02AEE |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22111247 |
|---|---|
| DOI: | 10.1016/j.celrep.2023.112696 |