VEGFA and lung carcinoma: Simvastatin is an HMGR antagonist and can reduce osteolytic bone metastases of lung cancers, potentially through the downregulation of CD44, P53, and MMPs438 or the antagonistic interaction between p53 and CD44.439 Furthermore, a thrombin inhibitor, argatroban, could reduce the bone metastasis of breast cancer cells by suppressing the activation of tissue factors and VEGF secretion.440 The ET axis is another promising therapeutic target for the treatment of prostate cancer bone metastases.