Elucidation of the plasticity of pancreatic cancer molecular subtypes and development of novel diagnostic and therapeutic approaches

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20819
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Nagoya University
• Principal Investigator: BABA TAISUKE 名古屋大学, 医学部附属病院, 病院助教 (30962782)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 膵癌 / 分子サブタイプ / エピジェネティクス

Outline of Final Research Achievements

In this study, we focused on TFFs (TFF1/TFF2/TFF3) as regulators of pancreatic cancer molecular subtype plasticity (Basal-like-to-classical shift) and examined the effects of these genes on the Classical program. In general, pancreatic cancer cell lines are strongly anchored to Basal-like subtype in 2D culture, so it is difficult to verify the Classical program in the conventional 2D culture. We established the Chicken Egg Chorioallantoic Membrane (CAM) Model and analyzed the function of these genes by inducing tumorigenesis in a short period of time. Our results suggest that TFF1 is a regulator of pancreatic cancer molecular subtypes.

Free Research Field

膵癌、胆道癌、エピジェネティクス、メタボロミクス、AI

Academic Significance and Societal Importance of the Research Achievements

膵癌のトランスクリプトーム解析から膵癌はClassicalとBasal-likeの二つの主要な分子サブタイプに分類されることが明らかとなった。一般的にClassicalサブタイプは予後がよく化学療法感受性良好、一方のBasal-likeは増殖・転移傾向があり、化学療法感受性が悪いことが知られている。Classical/Basal-like programの制御因子が同定されれば、化学療法の効きにくいBasal-likeサブタイプをClassicalサブタイプへと誘導し、化学療法感受性を飛躍的に向上させる新しい治療戦略が実現する。