Drug Response Analysis - Case Study
For a certain type of tyrosine kinase inhibitor, which shows great promise in the phase III clinical trials for a type of leukemia, a lower rate of complete recovery was observed in certain cases through unknown drug resistance mechanisms. In order to move forward with very promising therapy, the company needed to devise a strategy involving adjuvant drugs and/or objective biomarkers to identify responders up front.
Situation
As the compound was in phase III trials, the company had been working on the compound for many years. It had analysed a vast amount of clinical data including mutation profiling, RNA expression, immunophenotyping, phosphoprotein expression of key signaling molecules and drug response assays. Nevertheless they found it difficult to determine the underlying molecular mechanism and therefore work towards potential mitigation strategies.
Euretos Solution
We created a data driven multi-level molecular profile of responders and non-responders at various time points. Based on these detailed molecular profiles, we identified several mechanisms that may drive drug resistance. Based on these mechanisms we were identified a number of options for novel combination therapies. Also we suggested several potential novel biomarkers to classify patients based on expected drug response.
Results
The results of our investigation are now being implemented in further clinical trials where patients are better characterised up front and a number of potential combination therapies are investigated.
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