Evaluating response to antineoplastic drug combinations in tissue culture models
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Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
C Patrick Reynolds1, Barry J Maurer
1USC-CHLA Institute for Pediatric Clinical Research, University of Southern California and Childrens Hospital Los angeles, Los Angeles, CA, USA.
Abstract:
The mainstay of clinical antineoplastic chemotherapy is multiagent combinations, most of which were developed empirically. Because of the desire to speed research and decrease costs, there is increasing interest in moving new drugs into clinical trials in potentially active combinations based on preclinical testing data. Different mathematical models have been proposed for evaluating drug interactions, which can be classified as synergistic (combinations demonstrating greater than the additive activity expected from each agent alone), additive, or antagonistic (drugs showing less activity in combination than expected from the sum of each agent alone). Here, we briefly review some of the principles for testing cytotoxic drug interactions. We focus this review on application of the Combination Index method (as developed by Chou and colleagues) in the evaluation of drug interactions in cell culture assays.
Insights
This review covers principles for testing cytotoxic drug interactions, focusing on the Combination Index method. This approach aids in evaluating synergistic, additive, or antagonistic effects of antineoplastic chemotherapy drug combinations in cell cultures.
Area of Science:
- Pharmacology
- Cancer Research
- Drug Discovery
Background:
- Clinical antineoplastic chemotherapy relies heavily on multiagent drug combinations, often developed empirically.
- There is a growing need to accelerate research and reduce costs by using preclinical data to identify promising drug combinations for clinical trials.
Purpose of the Study:
- To review principles for testing cytotoxic drug interactions.
- To highlight the application of the Combination Index (CI) method for evaluating drug interactions in cell culture assays.
Main Methods:
- Review of mathematical models for evaluating drug interactions (synergistic, additive, antagonistic).
- Focus on the Combination Index (CI) method developed by Chou and colleagues.
- Application of CI method in cell culture assays for drug interaction evaluation.
Main Results:
- The Combination Index (CI) method provides a quantitative assessment of drug interactions.
- Synergistic interactions show greater than additive activity, while antagonistic interactions show less.
- Cell culture assays are a key platform for applying these interaction evaluation methods.
Conclusions:
- Empirical development of chemotherapy combinations is being supplemented by data-driven approaches.
- The Combination Index method is a valuable tool for preclinical evaluation of drug interactions in cancer research.
- Utilizing cell culture assays with methods like the CI score can optimize the selection of drug combinations for clinical trials.
