Inhibition of AXL and VEGF-A Has Improved Therapeutic Efficacy in Uterine Serous Cancer

Cancers

Hollie Noia¹  Katherine C. Fuh¹  Carolyn K. McCourt¹  Lindsay M. Kuroki¹  Danny Wilke¹  Michael D. Toboni¹  Matthew A. Powell¹  Andrea R. Hagemann¹  Premal H. Thaker¹  Elena Lomonosova¹  Mary M. Mullen¹  Alyssa Oplt¹  Jo’an I. Tankou¹  Shaina F. Bruce¹  Dineo Khabele¹  Angela Schab¹  David G. Mutch¹ 

[1] Barnes Jewish Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University, St. Louis, MO 63110, USA;

关键词: endometrial cancer;    uterine serous cancer;    bevacizumab;    recurrent endometrial cancer;    AXL inhibition;    AVB-500;   

DOI  :  10.3390/cancers13235877

来源: DOAJ

【 摘 要 】

Endometrial cancer remains the most prevalent gynecologic cancer with continued rising incidence. A less common form of this cancer is uterine serous cancer, which represents 10% of endometrial cancer cases. However, this is the most aggressive cancer. The objective was to assess whether inhibiting the receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve response in uterine serous cancer. To prove this, we conducted multiple angiogenesis assays including tube formation assays and angiogenesis invasion assays. In addition, we utilized mouse models with multiple cells lines and subsequently analyzed harvested tissue through immunohistochemistry CD31 staining to assess microvessel density. The combination treatment arms demonstrated decreased angiogenic potential in each assay. In addition, intraperitoneal mouse models demonstrated a significant decrease in tumor burden in two cell lines. The combination of AVB-500 and bevacizumab reduced tumor burden in vivo and reduced morphogenesis and migration in vitro which are vital to the process of angiogenesis.

【 授权许可】

Unknown