Genome Biology, 2016-04, Vol.17 (1), p.80-80, Article 80
2016
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- Autor(en) / Beteiligte
- Titel
- Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma
- Ist Teil von
- Genome Biology, 2016-04, Vol.17 (1), p.80-80, Article 80
- Ort / Verlag
- England: BioMed Central
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Intratumoral heterogeneity hampers the success of marker-based anticancer treatment because the targeted therapy may eliminate a specific subpopulation of tumor cells while leaving others unharmed. Accordingly, a rational strategy minimizing survival of the drug-resistant subpopulation is essential to achieve long-term therapeutic efficacy. Using single-cell RNA sequencing (RNA-seq), we examine the intratumoral heterogeneity of a pair of primary renal cell carcinoma and its lung metastasis. Activation of drug target pathways demonstrates considerable variability between the primary and metastatic sites, as well as among individual cancer cells within each site. Based on the prediction of multiple drug target pathway activation, we derive a combinatorial regimen co-targeting two mutually exclusive pathways for the metastatic cancer cells. This combinatorial strategy shows significant increase in the treatment efficacy over monotherapy in the experimental validation using patient-derived xenograft platforms in vitro and in vivo. Our findings demonstrate the investigational application of single-cell RNA-seq in the design of an anticancer regimen. The approach may overcome intratumoral heterogeneity which hampers the success of precision medicine.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1474-760X, 1474-7596eISSN: 1474-760XDOI: 10.1186/s13059-016-0945-9Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4852434
- Format
- –
- Schlagworte
- Adult, Animals, Bioinformatics, Breast cancer, Carcinoma, Renal Cell - drug therapy, Carcinoma, Renal Cell - genetics, Carcinoma, Renal Cell - pathology, Cells, Cultured, Cloning, Drug resistance, Gene expression, Gene Expression Profiling - methods, Genomes, Growth factors, Humans, Investigations, Kidney cancer, Kidney Neoplasms - drug therapy, Kidney Neoplasms - genetics, Kidney Neoplasms - pathology, Lung carcinoma, Lung Neoplasms - drug therapy, Lung Neoplasms - secondary, Male, Metabolism, Metastases, Metastasis, Mice, Molecular Targeted Therapy - methods, Mutation, Precision medicine, Principal components analysis, Renal cell carcinoma, Ribonucleic acid, RNA, Sequence Analysis, RNA - methods, Single-Cell Analysis - methods, Tumor cells, Tumors, Xenografts