EvoMaps: How cellular ecosystems drive early breast cancer evolution

Breast cancer develops from atypical hyperplasia, through ductal carcinoma in situ (DCIS) to invasive carcinoma. However, only few DCIS have potential to progress.

Since underlying evolutionary processes are largely unknown, the clinical prediction of progression is difficult, leading to a risk of over- and undertreatment for early breast cancer patients.In this project, we will develop EvoMaps as a novel analytical tool needed to overcome our knowledge gaps on the underlying spatial biology of subclonal expansion.

We hypothesize the existence of cellular ecosystems, where localized tumor-stroma interactions in synergy drive cancer progression and therapy resistance.

Hence, our overall objective is a reconstruction of the regulatory mechanisms of early breast cancer evolution, which we aim to accomplish through three specific aims:Decipher cellular ecosystems associated with progressive and radiotherapy-resistant features in a unique tissue series of early breast cancer.Identify the regulatory molecular mechanisms within these cellular ecosystems and how they drive early breast cancer progression and radiotherapy resistance using patient derived organoid models.Establish clinically relevant risk and treatment stratification models for early breast cancer patients.Importantly, our approach will reach beyond biological aspects and suggest also offer novel therapeutic modalities as well as a refined risk and treatment stratification of early breast cancer patients.