Doxycycline has been shown to inhibit the progression of metastases in osteosarcoma by downregulating the expression of MMPs, VEGF and Ezrin, suggesting that reprofiling of Doxycycline can prevent the evolvement of pulmonary micro-metastases to clinically detectable macro-metastases and suppress the lethal progress of Osteosarcoma by inhibiting the expression of MMPs, VEGFA and ezrin at primary sites (Hadjimichael et al., 2022; Fife et al., 1997). Here, VEGFA is linked to osteosarcoma.