Adapalene abrogates erlotinib-induced skin disorder by regulating proinflammatory cytokine production from human epidermal cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19452
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Kobe University
• Principal Investigator: TAMURA Daisuke 神戸大学, 医学部附属病院, 非常勤講師 (80646597)
• Research Collaborator: NAGANO Tatsuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: アダパレン / エルロチニブ / 非小細胞肺がん

Outline of Final Research Achievements

The purpose of this study is to elucidate the functional mechanism of adapalene in erlotinib-induced skin disorder. Erlotinib-induced skin toxicity was experimentally introduced into human skin keratinocyte (HaCaT) by using erlotinib with TNF α and IL1β. Effects of adapalene on the production of proinflammatory cytokine were analyzed by qRT-PCR. Effects of adapalene on the NFκB signaling pathway were analyzed by using a western blot. Effects of epithelial repair function of adapalene were analyzed by wound healing assay.
The mRNA levels of proinflammatory cytokines such as CCL2, CCL27, and IL8 in HaCaT were significantly suppressed by adapalene (P<0.05). Western blot suggested that erlotinib-induced phosphorylation of IκBα and p65 were decreased by adapalene. The expression of RARγ which inhibits NFκB pathway was increased by adapalene. In conclusion, these suggest that adapalene may be a possible candidate for the treatment of skin disorder induced by EGFR-TKI.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

EGFRチロシンキナーゼ阻害剤による皮膚毒性は頻度が高く、EGFRチロシンキナーゼ阻害剤の中止理由としても重要な有害事象の一つであるが、現在のところ、有効な治療法が少ない。本研究により、アダパレンの皮膚障害に対する有効性が明らかとなり、EGFRチロシンキナーゼが奏功しているものの、皮膚障害のために減量または中止せざるを得ない患者に対して大きな福音となり、生存率の改善に寄与することが期待される。