A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities.

Nature Communications
Ravi S NarayanBart A Westerman

Abstract

Personalized cancer treatments using combinations of drugs with a synergistic effect is attractive but proves to be highly challenging. Here we present an approach to uncover the efficacy of drug combinations based on the analysis of mono-drug effects. For this we used dose-response data from pharmacogenomic encyclopedias and represent these as a drug atlas. The drug atlas represents the relations between drug effects and allows to identify independent processes for which the tumor might be particularly vulnerable when attacked by two drugs. Our approach enables the prediction of combination-therapy which can be linked to tumor-driving mutations. By using this strategy, we can uncover potential effective drug combinations on a pan-cancer scale. Predicted synergies are provided and have been validated in glioblastoma, breast cancer, melanoma and leukemia mouse-models, resulting in therapeutic synergy in 75% of the tested models. This indicates that we can accurately predict effective drug combinations with translational value.

References

Aug 3, 2006·Nature Reviews. Drug Discovery·Janet E Dancey, Helen X Chen
Dec 8, 2006·The New England Journal of Medicine·Brian J DrukerUNKNOWN IRIS Investigators
Mar 3, 2007·Molecular Systems Biology·Joseph LehárCurtis T Keith
Dec 17, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael D PradosDaphne A Haas-Kogan
Jul 15, 2009·Clinical Breast Cancer·Carey K Anders, Lisa A Carey
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Caroline M EmeryLevi A Garraway
Mar 17, 2010·Cancer Treatment Reviews·John Araujo, Christopher Logothetis
Nov 26, 2010·Nature·Cory M JohannessenLevi A Garraway
Mar 25, 2011·Science Translational Medicine·Lecia V SequistJeffrey A Engelman
Apr 15, 2011·BMC Medical Genomics·Christopher A MillerAleksandar Milosavljevic
Sep 13, 2011·Genome Research·Giovanni CirielloNikolaus Schultz
Dec 14, 2011·The New England Journal of Medicine·José BaselgaGabriel N Hortobagyi
Mar 10, 2012·Molecular Cancer Therapeutics·Georgia HatzivassiliouMark R Lackner
Sep 21, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laurent SalphatiHeidi S Phillips
Oct 2, 2012·The New England Journal of Medicine·Keith T FlahertyJeffrey Weber
Dec 29, 2012·Molecular Cancer Therapeutics·Viola CarettiThomas Wurdinger
Jun 28, 2013·Nature·Charles L Sawyers
Nov 29, 2013·Nature·Benjamin Haibe-KainsJohn Quackenbush
Jun 3, 2014·Journal of Translational Medicine·Sandeep C PingleSantosh Kesari
Nov 25, 2014·Nature Biotechnology·Mukesh BansalUNKNOWN NCI-DREAM Community
Dec 3, 2014·Advances in Biological Regulation·Meena Jhanwar-UniyalRaj Murali
Mar 26, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bristi BasuUdai Banerji
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
Jun 9, 2015·Journal of Cheminformatics·Dávid BajuszKároly Héberger
Nov 12, 2015·Journal of Biomedical Nanotechnology·Dae Hwan ShinJin-Seok Kim
Nov 17, 2015·Nature·UNKNOWN Cancer Cell Line Encyclopedia Consortium, UNKNOWN Genomics of Drug Sensitivity in Cancer Consortium
May 7, 2016·Bioinformatics·Giovanni Y Di VeroliDuncan I Jodrell
Nov 3, 2016·Nature Reviews. Clinical Oncology·Juanita S Lopez, Udai Banerji
Jul 12, 2016·Cell·Francesco IorioMathew J Garnett
Jul 14, 2016·F1000Research·Zhaleh SafikhaniBenjamin Haibe-Kains
Aug 25, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fan LinOlaf van Tellingen
Jan 14, 2017·PLoS Computational Biology·Kaitlyn M GayvertOlivier Elemento
Sep 12, 2017·The New England Journal of Medicine·Georgina V LongJohn M Kirkwood

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Citations

Aug 28, 2021·Biomedicines·Nair LopesCarmen Jerónimo
Aug 28, 2021·International Journal of Molecular Sciences·Laura L ThompsonKirk J McManus
Jun 27, 2021·Molecular Cancer Therapeutics·Zilai WangLijun Rong
Sep 4, 2021·Briefings in Bioinformatics·Lianlian WuXiaochen Bo
Jan 22, 2022·Briefings in Bioinformatics·Weiping LinXiaochen Bo

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