Profiling the chromatome to scout for chromatin-associated metabolic vulnerabilities in triple negative breast cancer

Identifier:  TFG:2157

Handle: https://hdl.handle.net/20.500.11797/TFG2157

Authors:  García López, Laura del Carmen

Abstract:
The treatment of breast cancer is still a worldwide health challenge, due to the high intrinsic heterogeneity of the disease. There are four fundamental types of breast cancer, which are characterized by the expression of ER, PrR and/or HER2, or by the absence of all those three receptors (triple negative breast cancer). The triple negative is the most aggressive one because no targeted therapy has been found until now, fact that limits the treatment to non-selective and aggressive chemotherapeutic agents, and strongly reduces the probability of patient survival. In this project, we want to study the role of cancer metabolism in triple negative breast cancer with the final aim to identify a targeted therapy for this unmet medical need. The focus of our team is to study the role of cancer metabolism in epigenetic and transcriptional regulation. It has become evident during the last years that certain metabolic enzymes localize on chromatin despite their canonical cytoplasmic localization and function. We aim to study the role of metabolic enzymes specifically recruited on chromatin in breast cancer cells, to understand their contribution to tumour progression. For this, we set up a protocol for chromatin purification MScoupled, which allows us to investigate the chromatome of selected breast cancer cell lines recapitulating the different breast cancer phenotypes. By studying the chromatome of those cell lines, we will select enzymes specifically recruited to chromatin in triple negative breast cancer, and investigate what is their function there. The identification of a metabolic enzyme/pathway whose chromatin localization is selectively required in triple negative breast cancer could open up new possibilities for the successful treatment of this aggressive tumour.