Characterization and therapeutic repercussion of the ecology in HER2 positive breast cancer

Conditioned medium experiments carried out in our laboratory with CAFs derived from HER2-positive patients showed a significant capacity to promote resistance to trastuzumab plus pertuzumab therapies in two HER2-positive breast cancer cell lines (BCCLs), even in the presence of docetaxel. In order to elucidate the components of CAF-conditioned medium that would be relevant in the promotion of BCCL resistance, we performed a multi-omics strategy to identify miRNAs, cytokines, transcription factors and/or kinases in the secretome that target specific objectives in cancer cells. The combination of miRNA analysis, label-free LC-MS/MS quantification and cytokine arrays to explore the secretome of CAFs under treatment conditions revealed several up- and down-regulated candidates. We discuss the potential role of some of the most interesting candidates in generating resistance in HER2-positive breast cancer