Development of Precise Pharmocodiagnostic (PharmDx) Tests for Molecular Targeted Therapies

Tani, Yoichi; Hatanaka, Yutaka; Hashizume, Kaoru

doi:10.1267/ahc.38.209

Cited by 1 publication

(1 citation statement)

References 53 publications

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“…The second-generation oral and irreversible pan-HER tyrosine kinase inhibitors (TKI) dacomitinib and afatinib have very similar chemical structures and selectively bind to the ATP binding pockets of EGFR [2, 8,9]. These second-generation irreversible TKIs are considered clinically superior to first-generation reversible TKIs because they may block the activity of multiple receptors simultaneously and for a longer duration [4].…”

Section: Introductionmentioning

confidence: 99%

Localization and Accumulation Studies of Dacomitinib in Rat Intestines and Skin by Immunohistochemistry

Yamamoto

Saita

Oka

et al. 2019

Acta Histochem. Cytochem

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Dacomitinib, a second-generation tyrosine kinase inhibitor, was irreversible inhibitor forming covalent bonds with the kinase domains of EGFR and other ErbB family receptors. Dacomitinib has been approved for the treatment of locally advanced or metastatic nonsmall cell lung cancer. In this study, we aimed to develop an immunohistochemistry to detect dacomitinib-ErbB family receptor conjugates. Immunostaining was performed in rat intestine and skin tissues after oral administration of dacomitinib. Following a single oral dose of dacomitinib, strong staining was observed after 24 hr in the ileum and colon, with only slight staining in the duodenum and jejunum. In the skin, strong staining was observed in the epidermis, hair follicles, and sebaceous glands. Moreover, significant amounts of dacomitinib remained for up to 72 hr post-administration in the ileum, colon, and skin. This report is the first to elucidate the localization and accumulation of dacomitinib in the rat intestine and skin and should be valuable during efforts to clarify the mechanism dacomitinib-induced diarrhea or skin toxicities.

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Section: Introductionmentioning

confidence: 99%