The search of factor which regulate sensitivity to cetuximab focused on immunological alteration

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20625
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: University of Toyama (2018); St. Marianna University School of Medicine (2016-2017)
• Principal Investigator: Noguchi Akira 富山大学, 大学院医学薬学研究部(医学), 助教 (10456395)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: セツキシマブ / EGFR / 扁平上皮癌 / 口腔癌 / 頭頚部癌

Outline of Final Research Achievements

Cetuximab is the chimeric (mouse/human) monoclonal antibody which targetted epidermal growth factor receptor (EGFR). Despite its undeniable therapeutic value, we still do not fully understand the mechanisms of action responsible for cetuximab's anti-tumor effects in the head and neck squamous cancer (HNSCC). In this study, alterations in EGFR and its downstream genes in seven SCC cell lines (B-88, HSC-2, HSC-3, HSC-4, KOSC-2, SAS and A431) were assessed through next generation sequencing. The effect of cetuximab and HDACi, alone and in combination, on the viability of these cells were evaluated. As a result, the cells which indicated cetuximab resistance got susceptibility by treatment with HDACi.Morphologically cellular adhesion is decreased. The mRNA level of EGFR was elevated after treatment with HDACi. Our data suggested that combinations of cetuximab with HDAC inhibitor could be potential novel treatment strategies for HNSCC.

Free Research Field

口腔癌

Academic Significance and Societal Importance of the Research Achievements

頭頸部領域は解剖学的に生命活動にとって重要な臓器・感覚器が集中していることにより、治療の際には機能障害や容貌の変化をも見越した戦略が必要となっている。セツキシマブは非常に有用な化学療法剤であるが、その効果を予測する確立した因子は未だない。本研究はこれまで十分検討されていなかった免疫機構やエピジェネティックな変化に着目することにより、セツキシマブの作用機序の解明、新規のサロゲートマーカーの創出を目的とした。本研究結果からは、ある種のHDAC阻害剤を併用することで、セツキシマブの増強効果を示す可能性が示唆された。