THBS1 and metastatic melanoma: Several clinical trials applying THBS1-mimetics or analogs to enhance the inhibitory activity of THBS1 on vascularization failed to demonstrate beneficial efficacy in metastatic melanoma, advanced renal cell carcinoma, and soft tissue sarcoma13–15, suggesting that reduced vascularity induced by THBS1 may play a key role in creating a therapy-resistant microenvironment in aggressive tumors.