Investigation in the microenvironment of lung cancer and malignant pleural mesothelioma for the development of biomarker for the resistance to bevacizumab

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461191
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: GOTO Hisatsugu 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (00437641)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺癌 / 悪性胸膜中皮腫 / 血管新生阻害薬 / 薬剤耐性

Outline of Final Research Achievements

This study aimed to clarify the mechanism of resistance to anti-angiogenic therapy in cancer. Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. In this study, using mouse model of malignant pleural mesothelioma, we found that fibroblast growth factor (FGF) 2 played important role in the resistance to bevacizumab. We identified fibrocytes as the producer of FGF2 in the tumor tissue. In clinical specimens of lung cancer, the number of fibrocyte was significantly increased in bevacizumab-treated tumors, and is correlated with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocytes as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.

Free Research Field

呼吸器内科学