A Patient-Derived Xenograft Model Identifies AK1 as a Key Regulator of Metastatic Potential in Primary Triple-Negative Breast Cancer [WES]

Here, we leveraged patient-derived xenograft (PDX) models as a functional readout of primary tumor metastatic propensity. We first performed integrated genomic and transcriptomic profiling of primary breast tumors and their matched PDX models and found that key driver mutations, recurrent copy number alterations, and molecular subtype features were largely conserved between patient tumors and xenografts.

These findings support the utility of matched PDX models as clinically relevant platforms for studying tumor-intrinsic features associated with breast cancer progression. We next focused on TNBC PDX models with reproducible metastatic phenotypes across biological replicates and classified primary tumors into metastatic and non-metastatic groups based on their matched PDX behavior. Single-cell transcriptomic profiling of these tumors revealed that metastatic samples were characterized by hypoxia-associated metabolic reprogramming, with coordinated activation of hypoxia and glycolysis pathways.