Control of systemic progression of pancreatic cancer by blocking VCAM-1: a study of genetically-engineered mouse model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07584
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Saitama Medical University (2022); The University of Tokyo (2020-2021)
• Principal Investigator: Mizuno Suguru 埼玉医科大学, 医学部, 准教授 (30771050)
• Co-Investigator(Kenkyū-buntansha): 伊地知 秀明 東京大学, 医学部附属病院, 講師 (70463841)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵癌 / がん微小環境 / がん関連血栓塞栓症 / VCAM-1 / ANP

Outline of Final Research Achievements

Pancreatic cancer is the most lethal cancer. One of the poor prognostic factor is cancer-associated thromboembolism(CAT). We have established a genetically-engineered mouse model of pancreatic cancer that can recapitulate human disease. The model also frequently develops CAT. Treatment of the model with VCAM-1 neutralizing antibody strikingly prolonged the survival, which suggested that inhibition of CAT might have contributed to the prognosis. To clarify the underlying mechanisms, VCAM-1 knockout in the model was planned, however, due to the COVID-19 pandemic, crossing the mice is still ongoing. Instead, we found that VCAM-1 blockade prevented the systemic progression of CAT. In addition, advanced pancreatic cancer patients with CAT showed significantly high level of plasma VCAM-1 and ANP even before the CAT onset, which indicated that these can be promising biomarkers for defining the high risk group of CAT and for the patient selection to be treated with VCAM-1 inhibition therapy.

Free Research Field

消化器内科学　膵癌

Academic Significance and Societal Importance of the Research Achievements

最難治癌である膵癌において予後改善効果が期待できるVCAM-1阻害療法の機序として、予後不良因子である癌関連血栓症の進展を抑制することを見出し、血漿VCAM-1、ANP値が癌関連血栓症の高危険群およびVCAM-1阻害療法の対象患者選択のバイオマーカーとなる可能性を示した。実臨床に多い切除不能状態の進行膵癌患者においても予後を大きく改善させる可能性を示している。