Using ideas from evolutionary biology to identify drug resistance
Evolutionary-Informed Resistance Assays
EIRAs is a platform that uses ideas from evolutionary biology to help identify resistance to new cancer treatments in a pre-clinical setting. The technology is being developed by researchers working within the Centre for Evolution and Cancer at the Institute of Cancer Research (ICR).
Whilst resistance is the primary driver of failure to new treatments, we are continuously learning novel ways in which it can evolve in cancer. These diverse evolutionary routes mean identifying a molecular driver of resistance can prove challenging. EIRAs leverages theories from evolutionary biology alongside computational models to robustly identify resistance to a given cancer treatment.
Generate actionable information on drug resistance
Limit the Potential for Resistance Evolution
Support Decision Making
EIRAs will measure the evolution of cancer cells during exposure to a given compound to generate predictions for the propensity and mechanism of resistance. By better understanding how resistance will evolve to a new drug, EIRAs can provide valuable information to guide decision making at critical junctures in the drug development process.
Guide Pharmaceutical Design Decisions
By generating resistance to drug compounds during the early stages of drug development, EIRAs can reveal whether certain candidates have a higher propensity for resistance, simultaneously revealing the biology of the chosen target. This information can be combined with additional resources to help guide pharmaceutical design decisions, reducing the risk of resistance emergence in patients.
Current Limitations
Assays currently used to screen for promising compounds focus on the average behaviours of cell populations during a short timescale without confronting the longer-term issue of resistance. We believe these currently adopted assays ignore the heterogeneity of cancer cell populations which, when exposed to drug treatment, can provide indicators suggesting if and how resistance might evolve.
Test Novel Drug Combinations
The mechanisms of resistance to one drug can suggest evolutionary vulnerabilities that can be exploited by a second drug. EIRAs can help identify the best treatment combination to minimise the emergence of resistance in patients, maximising the success of new drugs whilst broadening the scope of existing ones.
EIRAs Techonology
The EIRAs platform combines genetic modifications of cancer cell line models with computational models that adopt theories from evolutionary biology to quantify the behaviour of cells when exposed to a drug. These measurements are used to generate predictions for the propensity and class of resistance to the given treatment, enabling direct comparisons between different candidate drugs.
Stratify Patient Populations
Characterising the molecular drivers of resistance to a novel drug pre-clinically can generate candidate biomarkers to predict resistance in patients. This information can help stratify patient populations during clinical trials, minimising the risk of trial failure.
About EIRAs
An Introduction
Meet EIRAs, a pioneering platform designed to identify resistance to new cancer treatments in a pre-clinical setting. Developed by visionary researchers at the Centre for Evolution and Cancer at the Institute of Cancer Research (ICR), EIRAs promises to unlock new insights into the complexities of cancer evolution.
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Meet our Team
Dr. Frederick Whiting
Prof. Trevor Graham
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