Bioinformatics Advance Access published online on October 8, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm447
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Successful anti-cancer drug targets able to pass FDA review demonstrate the identifiable signature distinct from the signatures of random genes and initially proposed targets.
1 CPA Global, LLC, 1725 Duke Street, Alexnadria, VA 22314 amayburd{at}cpaglobal.com tel:240-994-3091
2 IGMZ consulting, 456 Washington Ave, Belleville NJ 07109 tel: 973-4501982
3 Rush University Medical Center, Chicago Ill 60612, e-mail: James_L_Mulshine{at}rush.edu
*To whom correspondence should be addressed. James L. Mulshine, E-mail: James_L_Mulshine{at}rush.edu
 |
Abstract |
|---|
Motivation: New efforts to guide and prioritize the selection of cancer drug targets are urgently needed, as is evident by the slow development of novel anticancer agents and the narrow therapeutic index of existing drugs. Given these limitations, the current study was conducted to explore the classification features defining the therapeutic success that can result from targeting a particular gene.
Results: Classification was based on extracting features specific to known successful anticancer targets and combining them in a linear classifier, resulting in calculation of an enrichment score for each gene. Extended description, the search tool used in this study, enriched existing drug target candidates by up to 10-fold at a 
50% recall rate, covering 24000 genes or 80% of genome. More importantly, the target category with high attrition rate was classified from target category with low attrition rate, allowing to refine the drug development portfolios. Biological relevance of the parameters comprising the enrichment score was explored. Enrichment in cancer-specific effects was independently demonstrated by literature analysis. Imposing these enrichment scores on existing structural, pathway, and phenotype-based procedures for prospective target selection may enhance the efficiency and accuracy of target identification and accelerate drug design.
Availability: The software used in this work is available upon request.
Contact: amayburd{at}cpaglobal.com, James_L_Mulshine{at}rush.edu
Supplementary information: upplementary information is available at www.mayburd.com; http://www.rush.edu/rumc/page-1120170920643.html
Associate Editor: Dr.Jonathan Wren
Received on April 12, 2007; revised on July 30, 2007; accepted on August 25, 2007
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. M. Flanagan, J. M. Funes, S. Henderson, L. Wild, N. Carey, and C. Boshoff Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets Mol. Cancer Ther., January 1, 2009; 8(1): 249 - 260. [Abstract] [Full Text] [PDF]
|
|