Bevacizumab terminates HOXB9 induced tumor proliferation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293292
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Keio University
• Principal Investigator: Kitagawa Yuko 慶應義塾大学, 医学部, 教授 (20204878)
• Co-Investigator(Kenkyū-buntansha): Hasegawa Hirotoshi 慶應義塾大学, 医学部, 准教授 (00218455) ; Hayashida Tetsu 慶應義塾大学, 医学部, 講師 (80327543) ; Okabayashi Koji 慶應義塾大学, 医学部, 助教 (00338063)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 大腸癌 / HOXB9 / ベバシズマブ / 血管新生 / インターロイキン6

Outline of Final Research Achievements

Homeobox B9 (HOXB9), a transcriptional factor, regulates developmental processes and tumor progression and has recently been recognized as a strong angiogenic factor. This study aimed to investigate the role of HOXB9 in tumorigenesis and angiogenesis. Bevacizumab, an anti-VEGF antibody, remarkably suppressed tumor proliferation by inhibiting angiogenesis in HOXB9-overexpressing xenografts, and it improved overall survival and provided prolonged progression-free survival in HOXB9-overexpressing patients. HOXB9 promotes the secretion of angiogenic factors, including VEGF, to induce tumor proliferation through microenvironmental communication via IL6 signaling; moreover, silencing of VEGF or IL6 terminates microenvironmental crosstalk. Thus, HOXB9 and IL6 may be surrogate markers for bevacizumab treatment.

Free Research Field

外科学