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

@article{citeulike:4295928, abstract = {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.}, author = {Iorns, Elizabeth and Lord, Christopher J. and Grigoriadis, Anita and McDonald, Sarah and Fenwick, Kerry and Mackay, Alan and Mein, Charles A. and Natrajan, Rachael and Savage, Kay and Tamber, Narinder and Reis-Filho, Jorge S. and Turner, Nicholas C. and Ashworth, Alan}, citeulike-article-id = {4295928}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0005120}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19357772}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19357772}, day = {9}, doi = {10.1371/journal.pone.0005120}, issn = {1932-6203}, journal = {PloS one}, keywords = {biomarker, copy-number, drug\_discovery, gene\_expression, integration, rnai, target}, month = {April}, number = {4}, pages = {e5120+}, posted-at = {2009-11-03 17:11:01}, priority = {3}, publisher = {Public Library of Science}, title = {Integrated functional, gene expression and genomic analysis for the identification of cancer targets.}, url = {http://dx.doi.org/10.1371/journal.pone.0005120}, volume = {4}, year = {2009} }

TY - JOUR ID - citeulike:4295928 L3 - citeulike-article-id:4295928 N2 - 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. IS - 4 JF - PloS one SN - 1932-6203 TI - Integrated functional, gene expression and genomic analysis for the identification of cancer targets. PB - Public Library of Science VL - 4 SP - e5120 KW - biomarker KW - copy-number KW - drug_discovery KW - gene_expression KW - integration KW - rnai KW - target AU - Iorns, Elizabeth AU - Lord, Christopher AU - Grigoriadis, Anita AU - McDonald, Sarah AU - Fenwick, Kerry AU - Mackay, Alan AU - Mein, Charles AU - Natrajan, Rachael AU - Savage, Kay AU - Tamber, Narinder AU - Reis-Filho, Jorge AU - Turner, Nicholas AU - Ashworth, Alan PY - 2009/04/09/ UR - http://dx.doi.org/10.1371/journal.pone.0005120 ER -