AIM OF STUDY: Bevacizumab (BV) is broadly used to treat a number of cancers; however, BV resistance mechanisms and strategies to overcome this resistance are yet to be determined. MATERIALS AND METHODS: In this study, we used ovarian xenograft model to evaluate the underlying resistance mechanisms of BV in ovarian cancer treatment. RESULTS: Our results showed that EphB4 was overexpressed in BV-resistant xenograft models instead of other common receptor tyrosine kinases. In addition, when coadministrated with EphB4 blocker NVP-BHG712, the antitumor effect of BV was significantly enhanced in the resistant model, further confirmed the role of EphB4 in BV-resistant ovarian cancer. These results indicate that NVP-BHG712 reverses EphB4 overexpression-mediated resistance to BV. CONCLUSION: These findings represent a guide for the design of future medication strategy and may be useful in guiding the use of BV in combination with NVP-BHG712 in patients with resistance or intolerance ovarian cancer.
AIM OF STUDY: Bevacizumab (BV) is broadly used to treat a number of cancers; however, BV resistance mechanisms and strategies to overcome this resistance are yet to be determined. MATERIALS AND METHODS: In this study, we used ovarian xenograft model to evaluate the underlying resistance mechanisms of BV in ovarian cancer treatment. RESULTS: Our results showed that EphB4 was overexpressed in BV-resistant xenograft models instead of other common receptor tyrosine kinases. In addition, when coadministrated with EphB4 blocker NVP-BHG712, the antitumor effect of BV was significantly enhanced in the resistant model, further confirmed the role of EphB4 in BV-resistant ovarian cancer. These results indicate that NVP-BHG712 reverses EphB4 overexpression-mediated resistance to BV. CONCLUSION: These findings represent a guide for the design of future medication strategy and may be useful in guiding the use of BV in combination with NVP-BHG712 in patients with resistance or intolerance ovarian cancer.
Entities:
Keywords:
Bevacizumab; EphB4; ovarian cancer cells; xenograft
Authors: Dana M Roque; Eric R Siegel; Natalia Buza; Stefania Bellone; Dan-Arin Silasi; Gloria S Huang; Vaagn Andikyan; Mitchell Clark; Masoud Azodi; Peter E Schwartz; Gautam G Rao; Jocelyn C Reader; Pei Hui; Joan R Tymon-Rosario; Justin Harold; Dennis Mauricio; Burak Zeybek; Gulden Menderes; Gary Altwerger; Elena Ratner; Alessandro D Santin Journal: Br J Cancer Date: 2022-02-11 Impact factor: 7.640