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Clinical Research Programme

Breast Cancer Clinical Research Unit

Head of Unit:  Miguel Angel Quintela
Research highlights

Our studies about fatty acid synthase (FASN) have finally revealed a role for this molecule as a therapeutic target for preventing the development of epithelial cancers. FASN, an enzyme expressed at almost undetectable levels in adult tissues, elicits the metabolic impulse that cells undergoing the transformation process require to complete the transition from organised 2D-growth to de-organised, anchorage-independent 3D-growth. FASN inhibitors are well tolerated and have proven to abrogate the development of breast and lung cancers driven by oncogenes such as Pi3K, K-RAS or HER2. These findings set the grounds for future clinical interventions.

On the clinical side of our activities, in 2017, we launched 2 independent clinical trials addressing the adaptive mechanisms of escape against chronic exposure to antiangiogenics that our laboratory tackled between 2012 and 2016; the results were published last year. In one of the trials, CNIO-BR-008, we are exploring the concept of hypoxia-induced immunodepression. In a number of patients, instead of vascular normalisation, antiangiogenics deteriorate the vascular network, an occurrence associated with increased PD-L1 and kynurenine signalling; these patients can be detected by 18F-Misonidazole PET. In this trial we are exploring the therapeutic effect of adding MEDI-4736 (an anti-PD-L1 monoclonal antibody) to bevacizumab in breast cancer patients who experience disease progression while in treatment with bevacizumab monotherapy, stratified by MisoPET response. In the second trial, CNIO-BR-009, we are exploring the synergy between the mitochondrial inhibitor ME-344 and bevacizumab in patients who experience the opposite adaptive mechanism – vascular normalisation followed by mito-switch, detected by Miso-PET.