Revealing targeted therapy for human cancer by gene module maps

Cancer Research
David J WongHoward Y Chang

Abstract

A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here, we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor-prognosis "wound signature" is strongly associated with induction of both a mitochondria gene module and a proteasome gene module. We found that 3-bromopyruvic acid, which inhibits glycolysis, selectively killed breast cells expressing the mitochondria and wound signatures. In addition, inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed ...Continue Reading

References

May 1, 1990·Archives of Biochemistry and Biophysics·Y H Ko, B A McFadden
Aug 30, 2000·Nature·C M PerouD Botstein
Feb 2, 2002·Nature·Laura J van 't VeerStephen H Friend
Dec 20, 2002·The New England Journal of Medicine·Marc J van de VijverRené Bernards
Jun 27, 2003·The New England Journal of Medicine·Beverly S Mitchell
Jun 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Therese SorlieDavid Botstein
May 12, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M AyersL Pusztai
May 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jennifer PittmanMike West
May 27, 2004·Expert Review of Anticancer Therapy·Jean-Francois GeschwindPeter L Pedersen
Sep 28, 2004·Nature Genetics·Eran SegalAviv Regev
Feb 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Howard Y ChangMarc J van de Vijver
Jul 1, 2005·Molecular and Cellular Biology·Feng LiChi V Dang
Jul 29, 2005·Nature·Andy J MinnJoan Massagué
Oct 21, 2005·The New England Journal of Medicine·Martine J Piccart-GebhartUNKNOWN Herceptin Adjuvant (HERA) Trial Study Team
Oct 21, 2005·The New England Journal of Medicine·Edward H RomondNorman Wolmark
Nov 4, 2005·Nature·J Russell LipfordRaymond J Deshaies
Jan 13, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C H YangM Cristofanilli
Mar 7, 2006·Nature Genetics·Adam S AdlerHoward Y Chang
Oct 24, 2006·Nature Medicine·Anil PottiJoseph R Nevins

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Citations

Jul 6, 2011·Nature Reviews. Neurology·Gregory Riddick, Howard A Fine
Mar 27, 2010·Proceedings of the National Academy of Sciences of the United States of America·Xuelian Wei, Ker-Chau Li
Jul 17, 2008·Bioinformatics·Tae-Min KimYeun-Jun Chung
Oct 29, 2009·Carcinogenesis·Pamela K Kreeger, Douglas A Lauffenburger
Jan 26, 2011·The Cancer Journal·Rafael RosellJose Miguel Sanchez
Apr 9, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eduardo VilarStephen B Gruber
Nov 18, 2009·BMC Bioinformatics·Ugur DogrusozOzgun Babur
Mar 31, 2009·BMC Genomics·Paolo UvaEmanuele de Rinaldis
Oct 27, 2011·PLoS Computational Biology·David VenetVincent Detours
Apr 1, 2008·Expert Opinion on Medical Diagnostics·Peter Nygren, Rolf Larsson
Nov 1, 2009·Expert Opinion on Medical Diagnostics·Jia WeiRafael Rosell
Aug 22, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Dimitry S A NuytenMarc J van de Vijver
Aug 12, 2008·Current Opinion in Genetics & Development·Edison T Liu
Oct 11, 2008·Journal of Cellular Biochemistry·Carolyn M Klinge
Jun 6, 2015·BMC Medical Genomics·Liang YuLin Gao
Nov 22, 2012·Molecular Oncology·Muneyuki MasudaAndrew K Joe
Apr 10, 2008·Cell Stem Cell·David J WongHoward Y Chang
Aug 17, 2019·Chinese Journal of Integrative Medicine·Kang-Ning LiZhong Wang
Nov 29, 2012·Molecular Biology Reports·Ioannis A Voutsadakis
Jun 5, 2015·The Plant Journal : for Cell and Molecular Biology·Jiawei WangYijing Zhang
Sep 17, 2020·Cells·Sarah A JeffreysTherese M Becker
Feb 12, 2020·Nature Communications·Yutaka HashimotoIleana M Cristea
Sep 27, 2020·The Journal of Biological Chemistry·Qingqing LiuQiaoming Long
Jan 18, 2021·The Journal of Biological Chemistry·Qingqing LiuQiaoming Long

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