A versatile chemical tag that targets drugs to cancer tissue is reported in a study published in Nature Communications this week. The tag, which can in theory be attached to a variety of existing anti-cancer drugs and is removed in a two-step process by different types of tumour-associated enzymes, could increase the efficacy of anti-cancer therapies.
Two enzymes are required to remove the tag and release the drug, which is expected to occur predominantly in cancerous tissue, Nobuhide Ueki and colleagues report. Histone deacetylases control gene expression by removing acetyl groups from proteins and are often active in tumours and cathepsin L has been linked to tumour progression and metastasis. Removal of an acetyl group from the tag by histone deacetylases exposes a binding site that allows for subsequent cleavage by cathepsin L. The authors attach the tag to the anti-cancer drug puromycin and show that tagged puromycin is more effective than the free drug in inhibiting tumour growth in an animal model of colon cancer.