Abstract
In the post-genomic era, many researchers have taken a systematic approach to identifying abnormal genes associated with various diseases. However, the gold standard has not been established, and most of these abnormalities are difficult to be rehabilitated in real clinical settings. In addition to identifying abnormal genes, for a practical purpose, it is necessary to investigate abnormality diversity. In this context, this study is aimed to demonstrate simply restorable genes as useful drug targets. We devised the concept of "drug targetability" to evaluate several different modes of abnormal genes by predicting events after drug treatment. As a representative example, we applied our method to breast cancer. Computationally, PTPRF, PRKAR2B, MAP4K3, and RICTOR were calculated as highly drug-targetable genes for breast cancer. After knockdown of these top-ranked genes (i.e., high drug targetability) using siRNA, our predictions were validated by cell death and migration assays. Moreover, inhibition of RICTOR or PTPRF was expected to prolong lifespan of breast cancer patients according to patient information annotated in microarray data. We anticipate that our method can be widely applied to elaborate selection of novel drug tar...Continue Reading
References
Feb 3, 2005·Nature Reviews. Drug Discovery·Alexander Kamb
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Liat Ein-DorEytan Domany
Jun 15, 2006·Briefings in Bioinformatics·Christine Steinhoff, Martin Vingron
Nov 2, 2006·Genome Biology·Anne E CarpenterDavid M Sabatini
Jan 27, 2007·The Biochemical Journal·Greg M FindlayRichard F Lamb
Jan 19, 2008·Briefings in Bioinformatics·Dougu Nam, Seon-Young Kim
Feb 2, 2008·Science·Jose M SilvaKenneth Chang
Feb 2, 2008·Science·Michael R SchlabachStephen J Elledge
Jul 18, 2008·Bioinformatics·Min ZhangXia Li
Jan 24, 2009·Biochemical Pharmacology·Christian Bailly
Mar 10, 2009·Cell·Ji LuoStephen J Elledge
May 19, 2009·BMC Bioinformatics·Seon-Young Kim
Aug 12, 2009·Omics : a Journal of Integrative Biology·Jukka HiissaTero Aittokallio
Sep 9, 2010·Nature Medicine·Lee M Ellis, Isaiah J Fidler
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ivana BozicMartin A Nowak
Jun 10, 2011·Genome Research·Fabio VandinBenjamin J Raphael
Jul 16, 2011·Leukemia·H J M de JongeJ J Schuringa
Mar 31, 2012·Nature·Jordi BarretinaLevi A Garraway
Feb 27, 2013·PloS One·Xiao-Min WangMing Yao
Aug 29, 2013·Cancer Letters·Bingtian ZhaoYue Yang
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Oct 1, 2013·Cell Reports·Naif ZamanEdwin Wang
Oct 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Stephen R PiccoloW Evan Johnson
Mar 20, 2014·Scientific Reports·Jungsul LeeChulhee Choi
May 21, 2014·Oncology Reports·Xiaokai WangXiaochun Bai
Jul 22, 2014·Molecular Carcinogenesis·XianGuo ChenChaoZhao Liang
Aug 15, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yan FuNan Du
Sep 23, 2014·BMC Bioinformatics·Simon Kebede MeridAndrey Alexeyenko
Nov 2, 2014·PloS One·Elena A GoncharovaVera P Krymskaya
Jan 1, 2014·Scientific Data·Glenn S CowleyWilliam C Hahn
Citations
Oct 22, 2016·Protein Science : a Publication of the Protein Society·Douglas MarcotteLaura F Silvian
Jan 3, 2018·Neuro-oncology·Junseong ParkSeok-Gu Kang
Sep 17, 2019·Technology in Cancer Research & Treatment·Zhenjie BaiJicheng Zhou
Feb 23, 2018·Oncology Letters·Liankui HanDi Liu
Sep 13, 2018·Genes·JiaRui LiYu-Dong Cai