Novel biomarkers for EGFR inhibitors in gastroenterological cancers based on CGH analyses

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06754
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: National Cancer Center Japan (2016); Kinki University (2015)
• Principal Investigator: Togashi Yosuke 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (80758326)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: EGFR阻害剤 / 大腸癌 / 膵癌 / FGFRシグナル / PI3Kシグナル

Outline of Final Research Achievements

The CGH analysis has shown that FGF9, MAP3K10, and AKT2 genes can be related to the resistance to EGFR inhibitors. Using overexpressing cell lines, the resistance has been demonstrated in FGF9 and AKT2 genes, which can be cancelled by FGFR and PI3K inhibitors, respectively, but not in MAP3K10 gene.
In clinical samples, FGF9 amplification was observed at a frequency of 8/145 (5.5%) and tended to be related to wild-type KRAS (7/96, 7.3%). Furthermore, FGF9 amplification was not observed in any of the samples from the 15 responders to anti-EGFR therapies but was observed in one sample from the seven non-responders with wild-type KRAS. In addition, the difference was not significant, pancreatic cancer patients with high levels of Akt2 expression tended to have a poorer response and a shorter progression-free survival period after treatment with an EGFR inhibitor than those with low expression levels.

Free Research Field

腫瘍免疫・腫瘍ゲノム解析