Reference - Detail
| RRC ID | 58588 |
|---|---|
| Author | Su D, Zhang D, Jin J, Ying L, Han M, Chen K, Li B, Wu J, Xie Z, Zhang F, Lin Y, Cheng G, Li JY, Huang M, Wang J, Wang K, Zhang J, Li F, Xiong L, Futreal A, Mao W. |
| Title | Identification of predictors of drug sensitivity using patient-derived models of esophageal squamous cell carcinoma. |
| Journal | Nat Commun |
| Abstract |
Previous studies from the Cancer Cell Line Encyclopedia (CCLE) project have adopted commercial pan-cancer cell line models to identify drug sensitivity biomarkers. However, drug sensitivity biomarkers in esophageal squamous cell carcinoma (ESCC) have not been widely explored. Here, eight patient-derived cell lines (PDCs) are successfully established from 123 patients with ESCC. The mutation profiling of PDCs can partially recapture the tumor tissue actionable mutations from 161 patients with ESCC. Based on these mutations and relative pathways in eight PDCs, 46 targeted drugs are selected for screening. Interestingly, some drug and biomarker relationships are established that were not discovered in the CCLE project. For example, CDKN2A or CDKN2B loss is significantly associated with the sensitivity of CDK4/6 inhibitors. Furthermore, both PDC xenografts and patient-derived xenografts confirm CDKN2A/2B loss as a biomarker predictive of CDK4/6 inhibitor sensitivity. Collectively, patient-derived models could predict targeted drug sensitivity associated with actionable mutations in ESCC. |
| Volume | 10(1) |
| Pages | 5076 |
| Published | 2019-11-7 |
| DOI | 10.1038/s41467-019-12846-7 |
| PII | 10.1038/s41467-019-12846-7 |
| PMID | 31700061 |
| PMC | PMC6838071 |
| MeSH | Adult Aged Aminopyridines / therapeutic use* Biomarkers, Tumor / genetics Cell Line, Tumor Cyclin-Dependent Kinase 4 / antagonists & inhibitors Cyclin-Dependent Kinase 6 / antagonists & inhibitors Cyclin-Dependent Kinase Inhibitor p15 / genetics Cyclin-Dependent Kinase Inhibitor p16 / genetics Drug Resistance, Neoplasm Esophageal Neoplasms / drug therapy* Esophageal Neoplasms / genetics Esophageal Squamous Cell Carcinoma / drug therapy* Esophageal Squamous Cell Carcinoma / genetics Female Humans Male Middle Aged Piperazines / therapeutic use* Prognosis Protein Kinase Inhibitors / therapeutic use* Purines / therapeutic use* Pyridines / therapeutic use* Xenograft Model Antitumor Assays |
| IF | 12.121 |
| Times Cited | 2 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 15 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | TE-6(RCB1950) TE-8(RCB2098) TE-11(RCB2100) TE-14(RCB2101) TE-15(RCB1951) |