Integrated functional, gene expression and genomic analysis for the identification of cancer targets.

The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi) cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines...

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Autores principales:	Elizabeth Iorns, Christopher J Lord, Anita Grigoriadis, Sarah McDonald, Kerry Fenwick, Alan Mackay, Charles A Mein, Rachael Natrajan, Kay Savage, Narinder Tamber, Jorge S Reis-Filho, Nicholas C Turner, Alan Ashworth
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe6d4e18e3ac4117937a53debf5472d2
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spelling	oai:doaj.org-article:fe6d4e18e3ac4117937a53debf5472d22021-12-02T20:12:13ZIntegrated functional, gene expression and genomic analysis for the identification of cancer targets.1932-620310.1371/journal.pone.0005120https://doaj.org/article/fe6d4e18e3ac4117937a53debf5472d22009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19357772/?tool=EBIhttps://doaj.org/toc/1932-6203The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi) cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines with gene expression and genomic profiling to identify novel cancer targets. We performed parallel RNAi screens in multiple cancer cell lines to identify genes that are essential for viability in some cell lines but not others, suggesting that these genes constitute key drivers of cellular survival in specific cancer cells. This approach was verified by the identification of PIK3CA, silencing of which was selectively lethal to the MCF7 cell line, which harbours an activating oncogenic PIK3CA mutation. We combined our functional RNAi approach with gene expression and genomic analysis, allowing the identification of several novel kinases, including WEE1, that are essential for viability only in cell lines that have an elevated level of expression of this kinase. Furthermore, we identified a subset of breast tumours that highly express WEE1 suggesting that WEE1 could be a novel therapeutic target in breast cancer. In conclusion, this strategy represents a novel and effective strategy for the identification of functionally important therapeutic targets in cancer.Elizabeth IornsChristopher J LordAnita GrigoriadisSarah McDonaldKerry FenwickAlan MackayCharles A MeinRachael NatrajanKay SavageNarinder TamberJorge S Reis-FilhoNicholas C TurnerAlan AshworthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5120 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth Iorns Christopher J Lord Anita Grigoriadis Sarah McDonald Kerry Fenwick Alan Mackay Charles A Mein Rachael Natrajan Kay Savage Narinder Tamber Jorge S Reis-Filho Nicholas C Turner Alan Ashworth Integrated functional, gene expression and genomic analysis for the identification of cancer targets.
description	The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi) cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines with gene expression and genomic profiling to identify novel cancer targets. We performed parallel RNAi screens in multiple cancer cell lines to identify genes that are essential for viability in some cell lines but not others, suggesting that these genes constitute key drivers of cellular survival in specific cancer cells. This approach was verified by the identification of PIK3CA, silencing of which was selectively lethal to the MCF7 cell line, which harbours an activating oncogenic PIK3CA mutation. We combined our functional RNAi approach with gene expression and genomic analysis, allowing the identification of several novel kinases, including WEE1, that are essential for viability only in cell lines that have an elevated level of expression of this kinase. Furthermore, we identified a subset of breast tumours that highly express WEE1 suggesting that WEE1 could be a novel therapeutic target in breast cancer. In conclusion, this strategy represents a novel and effective strategy for the identification of functionally important therapeutic targets in cancer.
format	article
author	Elizabeth Iorns Christopher J Lord Anita Grigoriadis Sarah McDonald Kerry Fenwick Alan Mackay Charles A Mein Rachael Natrajan Kay Savage Narinder Tamber Jorge S Reis-Filho Nicholas C Turner Alan Ashworth
author_facet	Elizabeth Iorns Christopher J Lord Anita Grigoriadis Sarah McDonald Kerry Fenwick Alan Mackay Charles A Mein Rachael Natrajan Kay Savage Narinder Tamber Jorge S Reis-Filho Nicholas C Turner Alan Ashworth
author_sort	Elizabeth Iorns
title	Integrated functional, gene expression and genomic analysis for the identification of cancer targets.
title_short	Integrated functional, gene expression and genomic analysis for the identification of cancer targets.
title_full	Integrated functional, gene expression and genomic analysis for the identification of cancer targets.
title_fullStr	Integrated functional, gene expression and genomic analysis for the identification of cancer targets.
title_full_unstemmed	Integrated functional, gene expression and genomic analysis for the identification of cancer targets.
title_sort	integrated functional, gene expression and genomic analysis for the identification of cancer targets.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/fe6d4e18e3ac4117937a53debf5472d2
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Integrated functional, gene expression and genomic analysis for the identification of cancer targets.

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