Updated project metadata. Experiments were performed assessing whether targeting the pH regulatory proteins (CAIX, NHE1 and V-ATPase) that permit cancer cells to adapt to hypoxic conditions could produce an effective therapeutic response in breast cancer, using both 2D and 3D culture models. CAIX inhibitors were shown to combine effectively with irradiation in clonogenic assays. Proteomic-mass-spectrometric analysis was carried out to analyze the possible mechanisms through which the CAIX inhibitor used was combining with irradiation.