Localization of Sites of Osimertinib Action in Rat Intestine, Skin, and Lung by Immunohistochemistry

Acta Histochem Cytochem. 2023 Dec 28;56(6):145-151. doi: 10.1267/ahc.23-00055. Epub 2023 Dec 23.

Abstract

Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations and has shown efficacy in patients with non-small-cell lung cancer. In this study, we created osimertinib-specific antibodies and developed an immunohistochemistry (IHC) for locating the sites of osimertinib action. Moreover, we located osimertinib-protein conjugates in intestinal, dermal, and lung tissues of rats, thereby using our IHC to visualize the sites of the adverse effects of osimertinib, including diarrhea, skin disorder, and interstitial pneumonia. This report is the first to elucidate the localization of the sites of action of osimertinib in the rat intestine, skin, and lung and is expected to help clarify the mechanism of osimertinib-induced adverse effects.

Keywords: immunohistochemistry; intestine; lung; osimertinib; skin.