Role of Kras mutations in intestinal tumor progression

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18430
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Wakayama Medical University (2017); Japanese Foundation for Cancer Research (2016)
• Principal Investigator: Jun Oyanagi 和歌山県立医科大学, 医学部, 特別研究員 (80716069)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: オルガノイド / リキッドバイオプシー

Outline of Final Research Achievements

We established 42 organiod derived from surgically resected polyps from five familial adenomatous polyposis(FAP) patients. Comprehensive gene expression analysis revealed that some genes are differentially expressed between attenuated FAP(AFAP)-derived organoids and classical FAP(CFAP)-derived organoids. Drug sensitivity assay demonstrated that AFAP-derived KRAS mutant organoid are sensitive to MEK inhibitors although CFAP-derived KRAS mutant organoids are resistant. These data suggest that the differentially expressed genes regulate sensitivity to RAS signal inhibitors.
We explored predictive biomarkers for immune checkpoint inhibitors. Using multiplex assay system, 57 serum proteins were analyzed. We identified proteins associated with clinical benefits from nivolumab. We also identified proteins associated with onset of immune-related adverse events(irAEs). However, no overlapped proteins were identified between clinical benefits and irAE onset.

Free Research Field

腫瘍生物学