Discovery of druggable targets of colorectal cancers by genomic analysis with cancer stem-like cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Nagayama Satoshi 公益財団法人がん研究会, 有明病院 消化器外科, 医長 (70362499)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 大腸癌

Outline of Final Research Achievements

Aim) Using patient-derived cancer stem-like cell lines from resection samples of colorectal (CR) cancers (CRCs), this study is designed to discover a novel druggable target in the signaling pathway responsible for CRC pathogenesis by combining the drug effectiveness of various kinase inhibitors and the comprehensive proteogenomic analyses. Methods) Genomic mutations were identified by targetry sequencing using new-generation sequencer for 100 genes including KRAS, BRAF, PIK3CA, PTEN, APC and b-catenin which play critical roles in the CR carcinogenesis. Drug responses to various kinds of inhibitors including well-proven inhibitors against EGFR, VEGF, FGFR, mTOR, PI3K and MEK were assessed by in vitro analyses. Results) More than 30 patient-derived cell lines were established from resection samples. A heat map between the 30 different cancer stem-like cell lines with evidence of genomic mutations and the levels of drug sensitivity to the inhibitor library was created.

Free Research Field

消化器外科