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Topical Compound to Block EGFR Inhibitors May Ease Skin Toxicities, Study Finds

A topical treatment blocking the effects of EGFR inhibitors may limit skin toxicities caused by the targeted cancer therapy, a new study reports. EGFR inhibitors are increasingly used to treat advanced-stage epithelial cancers but can also affect other tissues like the skin where EGFR is expressed and affect patients' quality of life. In Science Translational Medicine, researchers from the Hebrew University of Jerusalem and elsewhere describe their use of a molecular screening approach to search for small molecules that block the binding of anti-EGFR monoclonal antibodies to EGFR, uncovering a candidate called SDT-011. Computational modeling suggested that SDT-011 binds to the same EGFR receptors as the inhibitors and a binding affinity assay found that when SDT-011 was bound to EGFR, there was 2,000-fold reduction in the affinity of Eli Lilly's EGFR inhibitor Erbitux (cetuximab). The researchers further developed a slow-release topical compound using nanoparticles to deliver SDT-011 preferentially to hair follicles. In a cell line assay and in an ex vivo model of human skin, the compound was effective in restoring EGFR signaling and, in an animal study, the compound appeared to be safe.