Targeting the niche of drug-tolerant tumor-repopulating cells to eradicate residual disease in breast cancer

Principal investigator:

Prof. Dr. vet. Sven Rottenberg, Vetsuisse Faculty, University of Bern. For more information, please visit the website.

Although various effective anti-cancer treatments have become available over the last decades, therapy resistance remains the major cause of death of cancer patients with disseminated tumors. Striking examples are patients with triple-negative breast cancer (TNBC), which are frequently defective in the repair of DNA double strand breaks, e.g. due to loss of BRCA1 function. Because of this defect, the patients initially show high response rates to DNA damage-inducing cancer therapy. Unfortunately, tumors are usually not eradicated by chemotherapy alone, and therapy-resistant tumor cells are eventually selected from residual primary or metastatic tumor sites. In this BCPM pilot project, we will address the problem of residual disease by applying state-of-the-art single cell sequencing technology combined with bulk RNASeq to understand and eventually target the underlying mechanisms. To this purpose, we will focus in the coming year on breast cancer patient-derived samples after neoadjuvant chemotherapy and combine the analysis with the study of residual disease in a genetically engineered mouse model for TNBC. With this pilot project, I propose a single cell sequencing-based approach that will take the analysis of cancer therapy resistance mechanisms to a new level and hopefully yield useful information for designing effective approaches to counteract therapy escape.