Visualizing evolution of resistance in breast cancer tumors through In Situ Sequencing

Intratumoral heterogeneity is a critical driver of tumor resistance, as varying populations of cancer cells within a tumor can exhibit different sensitivities to treatments.

This dynamic process of tumor response to therapy is most observable in the neoadjuvant setting, where chemotherapy, targeted therapy, or endocrine therapy is administered before surgery in cases of breast cancer.

We will apply an upgraded version of our Base-Specific In Situ Sequencing (BaSISS) method to follow the sub-clonal evolution of breast tumors in response to various treatment regimes, in different sub-set of cancers. We are particularly interested to characterize the subclones that resist treatment.

We will divide the project in a more explorative part, targeting a handful cases per subtype to identify potential resistance mechanisms and markers.

This will be followed by validation studies in larger patient cohorts (>50 cases), targeting these specific mechanisms and markers applying a smaller gene expression and cell-typing panel.

For the validation studies we will use our novel high-throughput, single cycle imaging OacISS (one active cycle ISS) method.

We hope to find new resistance markers that can be used to select a proper treatment, and resistance mechansims that can provide leads for developing new treatments.