Anti-angiogenic therapy in ovarian cancer: Current understandings and prospects of precision medicine

Abstract

Ovarian cancer (OC) remains the most fatal disease of gynecologic malignant tumors. Angiogenesis refers to the development of new vessels from pre-existing ones, which is responsible for supplying nutrients and removing metabolic waste. Although not yet completely understood, tumor vascularization is orchestrated by multiple secreted factors and signaling pathways. The most central proangiogenic signal, vascular endothelial growth factor (VEGF)/VEGFR signaling, is also the primary target of initial clinical anti-angiogenic effort. However, the efficiency of therapy has so far been modest due to the low response rate and rapidly emerging acquiring resistance. This review focused on the current understanding of the in-depth mechanisms of tumor angiogenesis, together with the newest reports of clinical trial outcomes and resistance mechanism of anti-angiogenic agents in OC. We also emphatically summarized and analyzed previously reported biomarkers and predictive models to describe the prospect of precision therapy of anti-angiogenic drugs in OC.

Efficacy and safety of anti-angiogenic drug monotherapy and combination therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials

“…Our research indicated that the combination of nintedanib and chemotherapy can improve PFS compared with chemotherapy alone or plus placebo. The combination of pazopanib and chemotherapy has been shown to provide higher ORR, which aligns with a previous meta-analysis (Zhang et al, 2023).…”

“…Bevacizumab achieves its therapeutic effect by preventing VEGF-A from engaging with VEGFR, resulting in the destruction of established vessels, interference with new vessel formation, and the reduction of intratumoral pressure ( Reinthaller, 2016 ). Research indicated that inhibiting VEGF signaling not only diminishes tumor vascularization but also aids in the morphological and functional normalization of the remaining vessels ( Mei et al, 2023 ). In addition, trebananib stands out as the sole angiopoietin inhibitor in our comprehensive analysis.…”

Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options

“…Bevacizumab-resistant mechanisms have been studied in different types of neoplasms and include pharmacodynamic tolerance, tachyphylaxis (i.e., acute decrease in response to a drug after a repetitive administration), alteration of the neovascular architecture, redundant angiogenic factors, induction of hypoxia, increased tumor invasiveness, and metastatic behavior [288,323,324]. Additionally, alterations in the ratio between VEGF-dependent and VEGF-independent vascular subtypes during antiangiogenic therapy led to resistance (Figure 4) [325].…”

Deregulated circRNAs in Epithelial Ovarian Cancer With Activity in PreclinicalIn VivoModels: Identification of Targets and New Modalities for Therapeutic Intervention

“…Angiogenesis plays an important role in generation and progression of EOC (146). Therefore, anti-angiogenic approaches play an important role in the treatment of EOC (147). Bevacizumab, which neutralizes VEGFA has been approved for treatment of EOC in various clinical scenarios (148).…”