Understanding the drivers of aggressive prostate cancer remains a major clinical challenge due to treatment-related confounding and disease heterogeneity. A key objective is to identify molecular programs associated with metastatic potential and how they interact with the tumor microenvironment.
We use de novo metastatic disease as a model to study progression in the absence of therapeutic pressure. By integrating bulk and single-cell transcriptomics, we have identified intrinsic transcriptional programs linked to metastatic potential in a treatment-naïve context.
In parallel, we investigate how alterations enriched in advanced disease, including PTEN loss, shape tumor behavior within its tissue context. Our analyses indicate that PTEN loss is associated with remodeling of the tumor microenvironment, including tumor–stroma communication, with potential implications for disease progression.
Our work, carried out in close collaboration with clinical teams and patient-derived cohorts, aims to understand how tumor programs, genetic alterations, and tissue context interact to drive aggressiveness within an evolutionary framework.