Unraveling carboplatin resistance mechanisms in triple negative breast cancer

Platinum-based chemotherapeutics induce pathological responses in many solid tumors. In breast cancer, their use is common in late metastatic patients. However, there is a growing interest to use carboplatin in (neo)adjuvant therapy regimens for triple negative breast cancer, a subtype characterized by its poor prognosis and limited treatment options. Patients develop resistance to platinum drugs over time, a process that is incompletely understood. Our aim is to identify molecular targets that mediate carboplatin resistance using state-of-the-art transcriptomics, genetic screening and drug screening techniques. By inhibiting specific targets that mediate carboplatin resistance in combination with carboplatin treatment, we hope to stave off the development of resistance. These combination therapies will be tested in state-of-the-art patient-derived tumor mouse models that reflect patient tumor heterogeneity and are better able to predict treatment response than conventional tumor models. Overall, this project promises to identify resistance mechanisms to carboplatin treatment in triple negative breast cancer and develop and validate combination therapies that overcome platinum resistance, improving the clinical benefit of this potent chemotherapeutic agent.