Statistical classification of treatment responses in mouse clinical trials for stratified medicine in oncology drug discovery
SAVEL, Helene
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
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Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
SAVEL, Helene
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
RICHERT, Laura
Statistics In System biology and Translational Medicine [SISTM]
Institut Bergonié [Bordeaux]
Bordeaux population health [BPH]
< Reduce
Statistics In System biology and Translational Medicine [SISTM]
Institut Bergonié [Bordeaux]
Bordeaux population health [BPH]
Language
EN
Article de revue
This item was published in
Scientific Reports. 2024-01-09, vol. 14, n° 1, p. 934
English Abstract
Translational oncology research strives to explore a new aspect: identifying subgroups that exhibit treatment response even during pre-clinical phases. In this study, we focus on PDX models and their implementation in mouse ...Read more >
Translational oncology research strives to explore a new aspect: identifying subgroups that exhibit treatment response even during pre-clinical phases. In this study, we focus on PDX models and their implementation in mouse clinical trials (MCT). Our primary objective was to identify subgroups with different treatment responses using Latent Class Mixed Model (LCMM).We used a public dataset and focused on one treatment, encorafenib, and two indications, melanoma and colorectal cancer, for which efficacy depends on a specific mutation BRAF V600E. One LCMM per indication was implemented to classify treatment responses at the PDX level, analyzing the growth kinetics of treated tumors and matched controls within the PDX models. A simulation study was carried out to explore the performance of LCMM in this context. For both applications, LCMM identified classes for which the higher the proportion of mutated BRAF V600E PDX models the greater the treatment effect, which is aligned with encorafenib use recommendations. The simulation study showed that LCMM could identify classes with large differences in treatment effects. LCMM is a suitable tool for MCT to explore treatment response subgroups of PDX. Once these subgroups are defined, characterization of their phenotypes/genotypes could be performed to explore treatment response predictors.Read less <