Computationally predicting clinical drug combination efficacy with cancer cell line screens and independent drug action.

Nature Communications
Alexander Ling, R Stephanie Huang

Abstract

Evidence has recently emerged that many clinical cancer drug combinations may derive their efficacy from independent drug action (IDA), where patients only receive benefit from the single most effective drug in a drug combination. Here we present IDACombo, an IDA based method to predict the efficacy of drug combinations using monotherapy data from high-throughput cancer cell line screens. We show that IDACombo predictions closely agree with measured drug combination efficacies both in vitro (Pearson's correlation = 0.93 when comparing predicted efficacies to measured efficacies for >5000 combinations) and in a systematically selected set of clinical trials (accuracy > 84% for predicting statistically significant improvements in patient outcomes for 26 first line therapy trials). Finally, we demonstrate how IDACombo can be used to systematically prioritize combinations for development in specific cancer settings, providing a framework for quickly translating existing monotherapy cell line data into clinically meaningful predictions of drug combination efficacy.

References

Nov 1, 2008·Cancer Research·Vincent T DeVita, Edward Chu
Jan 12, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nguyen TanLisa D Belmont
Feb 9, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A OcanaI F Tannock
Jul 15, 2015·Pharmacology Research & Perspectives·Julie Foucquier, Mickael Guedj
Dec 31, 2015·PloS One·Christian RitzDaniel Gerhard
Mar 8, 2016·PloS One·Vasileios A StamelosAlan Richardson
Mar 18, 2016·Molecular Cancer Therapeutics·Jennifer O'NeilStuart D Shumway
Jun 29, 2018·Pharmacology & Therapeutics·Alexander LingR Stephanie Huang
Aug 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A OcanaI F Tannock

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Citations

May 10, 2021·Advanced Drug Delivery Reviews·Nathaniel Sheng Hua TooEliza Li Shan Fong
Aug 4, 2021·Briefings in Bioinformatics·Liye HeTero Aittokallio

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Methods Mentioned

BETA
scraping

Software Mentioned

IDAcomboscore
drc R package
rvest
ALMANAC
IDA
IDACombo
rvest R package
Combo
drc R package R package
powerSurvEpi R package

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