Mechanisms of resistance to molecularly targeted drugs for oral squamous cell carcinoma and investigation of countermeasures

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11732
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tokai University
• Principal Investigator: YAMAZAKI Hiroshi 東海大学, 医学部, 准教授 (00338708)
• Co-Investigator(Kenkyū-buntansha): 森 泰昌 国立研究開発法人国立がん研究センター, 中央病院, 医員 (00296708)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 外科系歯学 / 臨床腫瘍学 / 口腔癌

Outline of Final Research Achievements

The expression of mutant epidermal growth factor receptor (EGFRvIII) was investigated in 96 patients with oral squamous cell carcinoma (OSCC) who underwent surgery. Biopsied tissue samples underwent reverse transcription polymerase chain reaction (PCR), Sanger sequencing, and digital PCR testing, as well as next-generation sequencing. The detection of EGFRvIII was not consistent among the cases, but at least 3 (3%) were considered definitely positive. In order to elucidate the functions of EGFRvIII, we used an OSCC cell line, prepared and evaluated cetuximab-resistant and EGFRvIII-transfected OSCC cell lines. We detected no changes in the protein expression of EGFRvIII, or the signal transduction pathway, in either line.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

上皮成長因子受容体（EGFR）の抗体であるセツキシマブ（Cmab）は、局所進行あるいは再発転移口腔癌（OSCC）の標準治療に用いられている。そのため、Cmabに関するバイオマーカーの確立は重要であるが、現在のところ真に有用なバイオマーカーは存在せず、これを発見することはきわめて重要である。Cmabは野生型に対する抗体であり、変異型であるEGFRvⅢへの結合性は低いため、EGFRvⅢを指標としたネガティブセレクションの可能性が示唆されている。