TY - JOUR
T1 - Objective assessment of cancer genes for drug discovery
AU - Patel, Mishal N.
AU - Halling-Brown, Mark D.
AU - Tym, Joseph E.
AU - Workman, Paul
AU - Al-Lazikani, Bissan
N1 - Funding Information:
This work was supported by Cancer Research UK (grant numbers C309/A8274 and C309/A11566). P.W. is a Cancer Research UK Life Fellow. The authors acknowledge additional funding from Cancer Research UK to the Cancer Research UK Cancer Centre and from the UK National Health Service (NHS) to the National Institute for Health Research (NIHR) Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden Hospital, UK. The authors thank K. Bulusu for technical help, and thank J. Blagg, M. Garnett and U. McDermott for valuable discussions and comments. Author contributions: B.A.L. conceived the project and designed the analysis; M.P., M.H.B. and B.A.L. performed the data analysis and informatics and wrote the paper; P.W. provided biological analysis and insights and wrote the paper; J.T. developed the target annotation tool.
PY - 2013/1
Y1 - 2013/1
N2 - Selecting the best targets is a key challenge for drug discovery, and achieving this effectively, efficiently and systematically is particularly important for prioritizing candidates from the sizeable lists of potential therapeutic targets that are now emerging from large-scale multi-omics initiatives, such as those in oncology. Here, we describe an objective, systematic, multifaceted computational assessment of biological and chemical space that can be applied to any human gene set to prioritize targets for therapeutic exploration. We use this approach to evaluate an exemplar set of 479 cancer-associated genes, reveal the tension between biological relevance and chemical tractability, and describe major gaps in available knowledge that could be addressed to aid objective decision-making. We also propose drug repurposing opportunities and identify potentially druggable cancer-associated proteins that have been poorly explored with Regard to the discovery of small-molecule modulators, despite their biological relevance.
AB - Selecting the best targets is a key challenge for drug discovery, and achieving this effectively, efficiently and systematically is particularly important for prioritizing candidates from the sizeable lists of potential therapeutic targets that are now emerging from large-scale multi-omics initiatives, such as those in oncology. Here, we describe an objective, systematic, multifaceted computational assessment of biological and chemical space that can be applied to any human gene set to prioritize targets for therapeutic exploration. We use this approach to evaluate an exemplar set of 479 cancer-associated genes, reveal the tension between biological relevance and chemical tractability, and describe major gaps in available knowledge that could be addressed to aid objective decision-making. We also propose drug repurposing opportunities and identify potentially druggable cancer-associated proteins that have been poorly explored with Regard to the discovery of small-molecule modulators, despite their biological relevance.
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U2 - 10.1038/nrd3913
DO - 10.1038/nrd3913
M3 - Article
C2 - 23274470
AN - SCOPUS:84871901456
SN - 1474-1776
VL - 12
SP - 35
EP - 50
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 1
ER -