Study of skin innate immune response in cutaneous adverse effects caused by molecular targeted agents

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16037
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Nara Medical University
• Principal Investigator: OMMORI RIE 奈良県立医科大学, 医学部, 特任助教 (20533722)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: EGFR阻害薬 / 分子標的治療薬 / 薬疹 / ざ瘡様皮疹 / 自然免疫応答 / 抗菌ペプチド / human β-defensin

Outline of Final Research Achievements

Epidermal growth factor receptor inhibitors (EGFRIs) are a well-established targeted therapy for several cancers, and these drugs frequently cause cutaneous adverse effects such as papulo-pustular eruptions. However, the mechanism of the reactions remains unclear. In the present study, we investigated whether EGFRIs have an influence on innate immune response in patients’ skin to reveal the pathological mechanism of cutaneous adverse reactions caused by EGFRIs. We found that human β-defensin(hBD)1 and hBD3 were significantly decreased in patients with papulo-pustular eruptions. Our results may suggest that a reduction in hBD contributes to the increased incidence of papulo-pustular eruptions.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、EGFR阻害薬によるざ瘡様皮疹発症にはβ-defensinが非常に強く関与し、β-defensin産生抑制効果が、EGFR阻害薬による皮膚症状の病態形成にかかわっている可能性が示唆された。このことから、将来的にはβ-defensin含有外用薬などにより患者皮膚局所のβ-defensinを補充することで、ざ瘡様皮疹の発症を予防できる可能性が示された。