When administered systemically in a hypoperfused pancreatic cancer mouse model at a low dose of cilengitide, MC‐T‐DOX readily acquired prolonged circulation time; its proangiogenic activity was specifically “turned on” in tumor vessels through cleavage by MT1‐MMP on tumor endothelial cells to release cilengitide. Here, MMP14 is linked to familial pancreatic carcinoma.