Upon exposure to CAF-secreted proteases, the shielding anionic E8 domain was removed, unmasking the cationic R8 cell-penetrating peptide and driving selective uptake into CAFs, resulting in a subsequent 70% reduction in intratumoral α-SMA+ CAFs, a marked decrease in ECM deposition, and a consequent rise in tumor oxygenation. This evidence concerns the gene ACTA1 and neoplasm.