The mutation effect of Ras-Raf-MAPK and PI3K/Akt pathway for chemosensitivity of cetuximab treatment in the oral cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 26463069
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Okayama University
• Principal Investigator: Konouchi Hironobu 岡山大学, 医歯薬学総合研究科, 准教授 (20294423)
• Co-Investigator(Renkei-kenkyūsha): MURAKAMI Jun 岡山大学, 岡山大学病院, 助教 (40362983)
• Research Collaborator: OKADA Shunsuke 岡山大学, 岡山大学病院, 医員 (00759681)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 口腔癌 / セツキシマブ / アービタックス / PET / BRAF / KRAS / NRAS / PIK3CA

Outline of Final Research Achievements

Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR), and is effective for tumors with overexpression of EGFR. It was originally used for metastatic colorectal cancer, but since the overexpression of EGFR is seen in 80-100% of head and neck cancer (HNC), antitumor effect is also expected in HNC. In this study, we have assessed the antitumor effect of Cetuximab treatment using 9 oral cancer cell lines, with regard to BRAF, KRAS, NRAS, PIK3CA mutation status. We found no mutation in the mutation hot spots of BRAF gene , KRAS gene, NRAS gene. We also evaluated 5 well-known hot spots of PIK3CA gene, E542K and H1047R mutations of PIK3CA gene were observed in Ca9-22 and HSG cells. BALB/c-nu mouse transplanted with PIK3CA mutated HSG cells showed in lower sensitivity for Cetuximab. The results suggest that E542K mutation of PIK3CA could be used as a screening test to evaluate the sensitivity of HNC to Cetuximab.

Free Research Field

歯科放射線学