Elucidation of the gastrointestinal NET pathogenesis through the DLL3 and its application to novel drug discovery

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16375
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka Medical College
• Principal Investigator: Kohei Taniguchi 大阪医科大学, 医学部, 講師 (70779686)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: DLL3 / 神経内分泌癌 / NET / NEC / 消化管NET

Outline of Final Research Achievements

We tried to clarify the gastrointestinal NEC (GI-NEC) pathogenesis through the DLL3 functions in this project. DLL3 has attracted interest as a novel molecular target in neuroendocrine carcinoma of the lung. Our results showed that DLL3 expression was extremely increased in the GI-NEC. Also, the knockdown of DLL3 suppressed the growth through the induction of apoptosis in GI-NEC cells. These findings suggested that DLL3 is one of the crucial molecules in GI-NEC. However, the development of the existing DLL3antibody-drug conjugate was suspended because of not overcoming standard treatment.
Hence, we conducted the establishment of a screening assay to extract the novel compound targeting DLL3.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

消化管神経内分泌腫瘍（癌）は、希少腫瘍に位置付けられ研究の進展が不十分な疾患であると認識している。本研究から、DLL3が同疾患で重要な役割を担っていることが同定され、新たな注目すべき分子を抽出することができた。また、DLL3の発現を抑制する新規化合物の探索するための実験系を構築することに取り組んだことにより、今後、消化管神経内分泌腫瘍の治療開発に繋がる成果を得ることが出来た。本研究から、本疾患の克服につながる土台が病態及び、治療の面から構築されたと考える。