Elucidation of chemoradiation therapy resistance mechanism using pancreatic cancer cell derived three-dimensional organoids

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19945
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kagoshima University
• Principal Investigator: KAWASAKI YOTA 鹿児島大学, 附属病院, 医員 (90770420)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 膵臓癌 / 化学療放射線感受性 / 抗酸化能力 / オルガノイドモデル / 食道癌

Outline of Final Research Achievements

We generated 3D organoids from biopsies representing tumors from therapy-negative esophageal cancer patients. Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%). Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P=0.0357).
The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

膵臓癌は極めて予後不良な消化器癌の一つであり、正しい個別化治療の選択が予後に作用する。今回、食道扁平上皮癌検体を用いた3D培養、オルガノイド形成に世界初で成功し、形成できたオルガノイドを用いた化学療法に対する奏功度が、実臨床と相関していたことは、食道癌個別化治療の確立に大きく寄与しうると考えられる。確立できた3D培養、オルガノイド形成方法を膵臓癌検体で利用することで、今後、膵臓癌個別化治療の確立にも大きく寄与しうる可能性がある。