Title |
Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma
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Published in |
Genome Biology, April 2016
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DOI | 10.1186/s13059-016-0945-9 |
Pubmed ID | |
Authors |
Kyu-Tae Kim, Hye Won Lee, Hae-Ock Lee, Hye Jin Song, Da Eun Jeong, Sang Shin, Hyunho Kim, Yoojin Shin, Do-Hyun Nam, Byong Chang Jeong, David G. Kirsch, Kyeung Min Joo, Woong-Yang Park |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Italy | 2 | 12% |
United States | 2 | 12% |
United Kingdom | 2 | 12% |
Austria | 1 | 6% |
Ireland | 1 | 6% |
Greece | 1 | 6% |
France | 1 | 6% |
Unknown | 7 | 41% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 53% |
Scientists | 7 | 41% |
Science communicators (journalists, bloggers, editors) | 1 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 2 | <1% |
Germany | 1 | <1% |
Norway | 1 | <1% |
United Kingdom | 1 | <1% |
Ghana | 1 | <1% |
Denmark | 1 | <1% |
United States | 1 | <1% |
Unknown | 296 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 74 | 24% |
Researcher | 61 | 20% |
Student > Master | 24 | 8% |
Student > Bachelor | 23 | 8% |
Student > Postgraduate | 15 | 5% |
Other | 49 | 16% |
Unknown | 58 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 79 | 26% |
Agricultural and Biological Sciences | 61 | 20% |
Medicine and Dentistry | 38 | 13% |
Computer Science | 14 | 5% |
Immunology and Microbiology | 11 | 4% |
Other | 33 | 11% |
Unknown | 68 | 22% |