It is likely, however, that tumour resistance to palbociclib occurs by multiple mechanisms, as evidenced by the breast cancer experience with the PALOMA-3 trial, which show no differential sensitivity to palbociclib based on PIK3CA mutation status.22 Additionally, the efficacy of CDK4/6 inhibitors in breast cancer occurred in combination with hormonal therapy, potentially highlighting the need to investigate combination therapy in UC. The gene discussed is PIK3CA; the disease is breast cancer.