Abstract
BackgroundBevacizumab combined with chemotherapy produces clinical durable response in 25–30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response and resistance to bevacizumab combination therapy.MethodsRecurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.ResultsBy comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non-responders 1 gene was significantly differentially expressed. In responders, this approach revealed 256 significantly differentially expressed genes (72 down- and 184 up-regulated genes at the time of progression). Genes differentially expressed in responders revealed a shift towards a more proneural and less mesenchymal phenotype at the time of progression.ConclusionsBevacizumab combination treatment demonstrated a significant impact on the transcriptional changes in responders; but only minimal changes in non-responders. This suggests that non-responding glioblastomas progress chaotically without following distinct gene expression changes while responding tumors adaptively respond or progress by means of the same transcriptional changes. In conclusion, we hypothesize that the identified gene expression changes of responding tumors are associated to bevacizumab response or resistance mechanisms.
Highlights
Bevacizumab combined with chemotherapy produces clinical durable response in 25–30% of recurrent glioblastoma patients
Responders were defined as patients with complete or partial response (CR + Partial response (PR)) and non-responders were defined as patients with stable disease (SD) or progressive disease (PD)
All patients had undergone relapse surgery prior to bevacizumab combination therapy but only half of the resected tumor samples were eligible for biomarker analysis
Summary
Bevacizumab combined with chemotherapy produces clinical durable response in 25–30% of recurrent glioblastoma patients. Bevacizumab, a VEGF targeting antibody, in combination with chemotherapy is among the most frequently used treatments in recurrent glioblastoma patients This treatment regimen has not proved active in the total population of recurrent glioblastoma patients [5], 25–30% of the patients achieve treatment response (defined as radiological and clinical improvement). This group of patients has demonstrated improved survival as well as quality of life [6,7,8,9], highlighting the importance of identifying predictive biomarkers for bevacizumab efficacy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
