Mapping Cellular Subpopulations within Triple Negative Breast Tumors Provides a Tool for Cancer Sensitization to Radiotherapy
Session type: Poster / e-Poster / Silent Theatre session
We propose a novel concept according to which TNBC sensitization to RT can be rationally-designed based on resolution of patient-specific intra-tumor subpopulations that emerge in response to RT treatment. The computational strategy we developed resolves the intra-tumor protein expression heterogeneity, measured by flow cytometry at the single cell level, and allows to break down a tumor into distinct subpopulations and the altered protein networks associated with each subpopulation. More specifically, a set of altered protein-protein correlation subnetworks is computed in each cell, namely cell specific signaling signature, which is used to divide the tumor mass into intra-tumor subpopulations.
Using mice models and patient derived TNBC tumors we show that two distinct subpopulations expanded in response to RT. We demonstrate that simultaneous targeting of central proteins representing those subpopulations, Her2 and cMet, was essential in order to sensitize TNBC to RT and stop its growth. The presented strategy can be broadly applicable.