Abstract
Simple SummaryUterine serous cancer (USC) is an aggressive form of endometrial cancer. USC constitutes less than 10% of endometrial cancer cases but is responsible for up to 40% of endometrial cancer deaths. Response to standard platinum and taxane therapy is modest, particularly in the recurrent setting. Thus, novel therapeutic strategies are needed to overcome this drug resistance. We hope that our findings provide strong preclinical support for the combination of an AXL inhibitor with bevacizumab in USC clinical trials in the recurrent setting.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.
Highlights
Endometrial cancer incidence continues to rise annually with an estimated 66,570 cases and 12,940 deaths predicted in the United States in 2021 [1]
Our objective is to determine whether inhibiting receptor tyrosine kinase AXL with AVB-500 in combination with bevacizumab would improve the response to the treatment of uterine serous cancer (USC)
To determine whether AXL affects key modulators of angiogenesis, we examined whether genetic or therapeutic inhibition of AXL would alter the expression of proangiogenic cytokines in culture media [36]
Summary
Endometrial cancer incidence continues to rise annually with an estimated 66,570 cases and 12,940 deaths predicted in the United States in 2021 [1]. The five-year overall survival (OS) for all endometrial cancers is over 80% since 75% of cases present with early stage disease. For the cases with extrauterine spread at time of diagnosis, survival significantly decreased [2]. Extrauterine spread at diagnosis has been reported in up to 70% of cases, which has a drastic effect on survival [3,4,5]. One of the most aggressive subtypes is uterine serous cancer (USC). USC accounts for only 10% of uterine cancer cases, it is responsible for 39% of uterine deaths making it the most deadly uterine cancer [6]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
