Treatment development targeting Hippo pathway for scirrhous type gastric cancer.

Authors

null

Yuichiro Miki

Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

Yuichiro Miki , Mami Yoshii , Kenji Kuroda , Hironari Miyamoto , Tatsuro Tamura , Takahiro Toyokawa , Shigeru Lee , Kiyoshi Maeda

Organizations

Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan, Osaka Metropolitan University Hospital, Osaka, Japan

Research Funding

JSPS-KAKENHI

Background: Treatment outcome of gastric cancer (GC) has been improved by minimally invasive surgery, and development of new drugs including immune checkpoint inhibitors. However, survival for patients with scirrhous type (SGC, Type4) gastric cancer is dismal. Methods: We collected miRNAs form exosomes released from cancer associated fibroblasts which is developed from resected gastric cancer tissue. Pathway enrichment analysis (PEA) of top miRNAs showed that they are significantly associated with Hippo signaling pathway (Hippo pathway). The molecules relating Hippo pathway was evaluated by Western blotting in cell line, and IHC of tissue array. Results: PEA using top miRNAs showed the significant relationship to Hippo pathway. Yap is a final effector in this pathway, and we found that YAP is not expressed in MKN45 cells (diffuse type), which is supposed to be degraded in cytoplasm. On the contrary, MKN74 cells express both YAP and pYAP. IHC showed that YAP translocation to nucleus is significantly associated with CTGF expression. CTGF low expression is significantly associated with worse prognosis especially in diffuse type GC (Log rank p = 0.022). This trend is similar in the analysis of patients with SGC. Conclusions: The role of Hippo pathway is different between intestinal type and diffuse type of GC. YAP activator could be effective for the treatment of SGC, and we are focusing on the treatment development.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2024 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Cancers of the Esophagus and Stomach and Other Gastrointestinal Cancers

Track

Esophageal and Gastric Cancer,Other GI Cancer

Sub Track

Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 42, 2024 (suppl 3; abstr 398)

DOI

10.1200/JCO.2024.42.3_suppl.398

Abstract #

398

Poster Bd #

K3

Abstract Disclosures

Similar Abstracts

Abstract

2023 ASCO Gastrointestinal Cancers Symposium

Identification of HER2+ malignant cells in gastric tumors from single-cell RNAseq data.

First Author: Zhiming Zhang

Abstract

2022 ASCO Gastrointestinal Cancers Symposium

Association of leptin with migration, invasion, and cancer stem-like properties in gastric cancer cells.

First Author: Ki Bum Park

Abstract

2023 ASCO Gastrointestinal Cancers Symposium

The effect of potassium-competitive acid blocker tegoprazan on gastric cancer cells.

First Author: Sang Kil Lee