Preventing skin toxicities induced by EGFR inhibitors by topically blocking drug-receptor interaction

Nethanel Friedman ¹ Liza Weinstein-Fudim ^2,3 Yelena Mostinski ² Jhonatan Elia ⁴ Sherri Cohen ² Eliana Steinberg ¹ Shoshana Frankenburg ^2,5 Tamar Peretz ² Galit Eisenberg ^2,5 Michal Lotem ^2,5 Ofra Benny ¹ Sharon Merims ^2,5

¹The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel
²Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Israel
³Laboratory of Teratology, Department of Medical Neurobiology, The Faculty of Medicine, Hebrew University of Jerusalem, Israel
⁴Department of Plastic and Reconstructive Surgery, Hadassah Medical Center, Hebrew University of Jerusalem
⁵Wohl Institute for Translational Medicine, Hadassah Medical Organization, Israel

EGFR inhibitors induce severe debilitating skin toxicities in the majority of treated patients. These side effects lead to a deterioration in the quality of life of the patients and compromise the anticancer treatment. Current treatment strategies for these skin toxicities are of limited benefit, focusing on symptom reduction rather than preventing the initial trigger that causes the toxicity. In this study, we present a novel compound and method for treating `on target` skin toxicity by blocking the drug only at the site of toxicity, without reducing the systemic dose reaching the tumor. Our innovation combines specific small molecules that are topically applied and delivered via a slow-release system derived from biodegradable nanoparticles that penetrate the hair follicles and sebaceous glands that are dense with EGFR. Our new approach has the potential to reduce skin toxicity and may in the future allow more cancer patients to continue their daily lives during treatment.