Understanding tumour growth variability in breast cancer xenograft models identifies PARP inhibition resistance biomarkers.

ABSTRACT: Understanding the mechanisms of resistance to PARP inhibitors (PARPi) is a clinical priority, especially in breast cancer. We developed a novel mathematical framework accounting for intrinsic resistance to olaparib, identified by fitting the model to tumour growth metrics from breast cancer patient-derived xenograft (PDX) data. Pre-treatment transcriptomic profiles were used with the calculated resistance to identify baseline biomarkers of resistance, including potential combination targets. The model provided both a classification of responses, as well as a continuous description of resistance, allowing for more robust biomarker associations and capturing the observed variability. Thirty-six resistance gene markers were identified, including multiple homologous recombination repair (HRR)

SUBMITTER: Voulgarelis D 

PROVIDER: S-EPMC11574300 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature