Analysis of the clinical influence of Hegehog signaling activation in melanoma.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08679
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Keio University
• Principal Investigator: Tanese Keiji 慶應義塾大学, 医学部(信濃町), 非常勤講師 (70464815)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 悪性黒色腫 / Hedgehogシグナル伝達経路

Outline of Final Research Achievements

Although various treatment options for malignant melanoma have become available in recent years, the number of cases that are cured is not large. Therefore, it is necessary to elucidate the molecular biological characteristics of the tumor that are different from those of existing therapeutic targets. We focused on the Hedgehog signaling pathway (HH signaling) and explored immunostaining methods to demonstrate that the HH signaling is activated in histopathological specimens. As a result, we found an antibody that can produce stained images of GLI1, a transcription factor of the Hedgehog signaling pathway, in the nucleus by using basal cell carcinoma tissues. Using this antibody in 180 malignant melanoma tumors, 30 samples (16.7%) showed activation of this signal not only in the tumor cells but also in the surrounding stroma.

Free Research Field

悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

悪性黒色腫ではMAPKシグナル伝達経路やAKTシグナル伝達経路、Wnt-βカテニンシグナル伝達経路が主なシグナル伝達経路として報告されており、これらを標的とした治療が社会実装もしくは開発段階にあるが、これらの治療をもってしても腫瘍が消退しない症例が少なからず存在する。本検討の結果、悪性黒色腫の一部の症例ではHHシグナルが活性化していることが確認でき、既知の悪性黒色腫で活性化しているシグナル伝達経路以外のシグナル伝達経路を標的とした治療開発が必要であることが示唆された。