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Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma

The emerging targeted therapies have revolutionized the treatment of advanced clear cell renal cell carcinoma (ccRCC) over the past 15 years. Nevertheless, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, larg...

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Autores principales: Liu, Zhicheng, Lin, Dongxu, Zhou, Yi, Zhang, Linmeng, Yang, Chen, Guo, Bin, Xia, Feng, Li, Yan, Chen, Danyang, Wang, Cun, Chen, Zhong, Leng, Chao, Xiao, Zhenyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345903/
https://www.ncbi.nlm.nih.gov/pubmed/35918352
http://dx.doi.org/10.1038/s41598-022-16657-7
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author Liu, Zhicheng
Lin, Dongxu
Zhou, Yi
Zhang, Linmeng
Yang, Chen
Guo, Bin
Xia, Feng
Li, Yan
Chen, Danyang
Wang, Cun
Chen, Zhong
Leng, Chao
Xiao, Zhenyu
author_facet Liu, Zhicheng
Lin, Dongxu
Zhou, Yi
Zhang, Linmeng
Yang, Chen
Guo, Bin
Xia, Feng
Li, Yan
Chen, Danyang
Wang, Cun
Chen, Zhong
Leng, Chao
Xiao, Zhenyu
author_sort Liu, Zhicheng
collection PubMed
description The emerging targeted therapies have revolutionized the treatment of advanced clear cell renal cell carcinoma (ccRCC) over the past 15 years. Nevertheless, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles from ccRCC cohorts were explored for integrative analysis. A credible method was developed to identify synthetic lethality (SL) pairs and a list of 72 candidate pairs was determined, which might be utilized to selectively eliminate tumors with genetic aberrations using SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medical targets for patients with BAP1 mutations. After mapping these target genes to the comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potentials in the BAP1 mutant tumors. Overall, our findings provided insight into the overview of ccRCC mutation patterns and offered novel opportunities for improving individualized cancer treatment.
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spelling pubmed-93459032022-08-04 Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma Liu, Zhicheng Lin, Dongxu Zhou, Yi Zhang, Linmeng Yang, Chen Guo, Bin Xia, Feng Li, Yan Chen, Danyang Wang, Cun Chen, Zhong Leng, Chao Xiao, Zhenyu Sci Rep Article The emerging targeted therapies have revolutionized the treatment of advanced clear cell renal cell carcinoma (ccRCC) over the past 15 years. Nevertheless, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles from ccRCC cohorts were explored for integrative analysis. A credible method was developed to identify synthetic lethality (SL) pairs and a list of 72 candidate pairs was determined, which might be utilized to selectively eliminate tumors with genetic aberrations using SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medical targets for patients with BAP1 mutations. After mapping these target genes to the comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potentials in the BAP1 mutant tumors. Overall, our findings provided insight into the overview of ccRCC mutation patterns and offered novel opportunities for improving individualized cancer treatment. Nature Publishing Group UK 2022-08-02 /pmc/articles/PMC9345903/ /pubmed/35918352 http://dx.doi.org/10.1038/s41598-022-16657-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Zhicheng
Lin, Dongxu
Zhou, Yi
Zhang, Linmeng
Yang, Chen
Guo, Bin
Xia, Feng
Li, Yan
Chen, Danyang
Wang, Cun
Chen, Zhong
Leng, Chao
Xiao, Zhenyu
Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
title Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
title_full Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
title_fullStr Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
title_full_unstemmed Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
title_short Exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
title_sort exploring synthetic lethal network for the precision treatment of clear cell renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345903/
https://www.ncbi.nlm.nih.gov/pubmed/35918352
http://dx.doi.org/10.1038/s41598-022-16657-7
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