A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities

Ravi S. Narayan, Piet Molenaar, Jian Teng, Fleur M. G. Cornelissen, Irene Roelofs, Renee Menezes, Rogier Dik, Tonny Lagerweij, Yoran Broersma, Naomi Petersen, Jhon Alexander Marin Soto, Eelke Brands, Philip Kuiken, Maria C. Lecca, Kristiaan J. Lenos, Sjors G. J. G. In ‘t Veld, Wessel Wieringen, Frederick F. Lang, Erik Sulman, Roel Verhaak, Brigitta G. Baumert, Lucas J. A. Stalpers, Louis Vermeulen, Colin Watts, David Bailey, Ben J. Slotman, Rogier Versteeg, David Noske, Peter Sminia, Bakhos A. Tannous, Tom Wurdinger, Jan Koster and Bart A. Westerman ()
Additional contact information
Ravi S. Narayan: Amsterdam UMC, location VUMC, Cancer Center
Piet Molenaar: Academic Medical Center
Jian Teng: Massachusetts General Hospital and Harvard Medical School
Fleur M. G. Cornelissen: Amsterdam UMC, location VUMC, Cancer Center
Irene Roelofs: Amsterdam UMC, location VUMC, Cancer Center
Renee Menezes: Netherlands Cancer Institute
Rogier Dik: Amsterdam UMC, location VUMC, Cancer Center
Tonny Lagerweij: Amsterdam UMC, location VUMC, Cancer Center
Yoran Broersma: Amsterdam UMC, location VUMC, Cancer Center
Naomi Petersen: Amsterdam UMC, location VUMC, Cancer Center
Jhon Alexander Marin Soto: Amsterdam UMC, location VUMC, Cancer Center
Eelke Brands: Amsterdam UMC, location VUMC, Cancer Center
Philip Kuiken: Amsterdam UMC, location VUMC, Cancer Center
Maria C. Lecca: Amsterdam UMC, location AMC, Cancer Center
Kristiaan J. Lenos: Amsterdam UMC, location AMC, Cancer Center
Sjors G. J. G. In ‘t Veld: Amsterdam UMC, location VUMC, Cancer Center
Wessel Wieringen: Amsterdam UMC, location VUMC
Frederick F. Lang: The University of Texas MD Anderson Cancer Center
Erik Sulman: NYU Langone Health
Roel Verhaak: The Jackson Laboratory for Genomic Medicine
Brigitta G. Baumert: Kantonsspital Graubünden, Loëstrasse 170
Lucas J. A. Stalpers: Academic Medical Center
Louis Vermeulen: Amsterdam UMC, location AMC, Cancer Center
Colin Watts: University of Birmingham, Edgbaston
David Bailey: IOTA Pharmaceuticals Ltd, St Johns Innovation Centre, Cowley Road
Ben J. Slotman: Amsterdam UMC, location VUMC, Cancer Center
Rogier Versteeg: Academic Medical Center
David Noske: Amsterdam UMC, location VUMC, Cancer Center
Peter Sminia: Amsterdam UMC, location VUMC, Cancer Center
Bakhos A. Tannous: Massachusetts General Hospital and Harvard Medical School
Tom Wurdinger: Amsterdam UMC, location VUMC, Cancer Center
Jan Koster: Academic Medical Center
Bart A. Westerman: Amsterdam UMC, location VUMC, Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16735-2

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DOI: 10.1038/s41467-020-16735-2

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