Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism

Muhammad Kashif; Claes Andersson; Sharmineh Mansoori; Rolf Larsson; Peter Nygren; Mats G. Gustafsson

doi:10.18632/oncotarget.21895

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

Research Papers:

Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism

Muhammad Kashif, Claes Andersson, Sharmineh Mansoori, Rolf Larsson, Peter Nygren and Mats G. Gustafsson _

PDF | HTML | Supplementary Files | How to cite

Oncotarget. 2017; 8:103952-103967. https://doi.org/10.18632/oncotarget.21895

Metrics: PDF 2240 views | HTML 5795 views | ?

Abstract

Muhammad Kashif1,3, Claes Andersson1, Sharmineh Mansoori1, Rolf Larsson1, Peter Nygren2 and Mats G. Gustafsson1

1Department of Medical Sciences, Cancer Pharmacology, and Computational Medicine, Uppsala University Academic Hospital, Uppsala, Sweden

2Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden

3Current/Present address: Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden

Correspondence to:

Mats G. Gustafsson, email: [email protected]

Keywords: synergy analysis; combinations; iso-genic; COMBIA; R package

Received: March 13, 2017 Accepted: September 03, 2017 Published: October 19, 2017

ABSTRACT

We analyzed survival effects for 15 different pairs of clinically relevant anti-cancer drugs in three iso-genic pairs of human colorectal cancer carcinoma cell lines, by applying for the first time our novel software (R package) called COMBIA. In our experiments iso-genic pairs of cell lines were used, differing only with respect to a single clinically important KRAS or BRAF mutation. Frequently, concentration dependent but mutation independent joint Bliss and Loewe synergy/antagonism was found statistically significant. Four combinations were found synergistic/antagonistic specifically to the parental (harboring KRAS or BRAF mutation) cell line of the corresponding iso-genic cell lines pair.

COMBIA offers considerable improvements over established software for synergy analysis such as MacSynergy^TM II as it includes both Bliss (independence) and Loewe (additivity) analyses, together with a tailored non-parametric statistical analysis employing heteroscedasticity, controlled resampling, and global (omnibus) testing.

In many cases Loewe analyses found significant synergistic as well as antagonistic effects in a cell line at different concentrations of a tested drug combination. By contrast, Bliss analysis found only one type of significant effect per cell line.

In conclusion, the integrated Bliss and Loewe interaction analysis based on non-parametric statistics may provide more robust interaction analyses and reveal complex patterns of synergy and antagonism.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 21895

Publication Alerts

Research Papers:

Bliss and Loewe interaction analyses of clinically relevant drug combinations in human colon cancer cell lines reveal complex patterns of synergy and antagonism

Abstract