Bevacizumab in ovarian cancer therapy: current advances, clinical challenges, and emerging strategies

Abstract

Bevacizumab targets the vascular endothelial growth factor signaling pathway, inhibiting tumor angiogenesis and reshaping the tumor microenvironment, positioning it as a cornerstone in ovarian cancer management. Its mechanisms of action include blocking VEGF-A-induced endothelial cell proliferation, promoting vascular normalization, alleviating hypoxic conditions, and reversing immunosuppression. Key phase III clinical trials, including GOG-0218, AURELIA, and PAOLA-1, have demonstrated that Bevacizumab significantly extends progression-free survival in the maintenance treatment of newly diagnosed advanced ovarian cancer, platinum-sensitive or resistant recurrent disease, and HRD-positive patients, with a median PFS of up to 37.2 months. However, its impact on overall survival remains limited, and challenges such as drug resistance, treatment-related toxicities, and high costs persist. Future advancements will hinge on multidisciplinary innovation, including dual-targeting approaches such as VEGF/Ang-2 bispecific antibodies, combination immunotherapies, intelligent nanodrug delivery systems, and AI-driven dynamic biomarker stratification. The use of biosimilars and adaptive platform trials offers promise in reducing costs and improving accessibility. These technological innovations mark a shift in ovarian cancer treatment from traditional chemotherapy to precision medicine, presenting new opportunities to improve long-term patient survival.

Keywords: bevacizumab; drug resistance; nanodrug delivery; ovarian cancer; tumor angiogenesis.

FIGURE 1

Mechanism of Bevacizumab in OC: VEGF Signaling Blockade and TME Remodeling. (A) Bevacizumab binds VEGF-A, preventing its interaction with VEGFR-1/2 on endothelial cells. This inhibits downstream pro-angiogenic signaling (Ras/ERK and PI3K/AKT pathways), resulting in endothelial apoptosis and regression of immature blood vessels. (B) In the TME, Bevacizumab induces vascular normalization by enhancing tight endothelial junctions and pericyte coverage, reducing hypoxia and acidosis, and reprograming immunosuppressive components, including converting M2 macrophages to M1 phenotypes and increasing CD8⁺ T cell infiltration. These changes improve chemotherapy delivery and anti-tumor immunity. This figure was created by Figdraw (https://www.figdraw.com).

FIGURE 2

Timeline of Key Clinical Trials and FDA Approvals for Bevacizumab in OC. Abbreviations: PLD, Pegylated Liposomal Doxorubicin; PTX, Paclitaxel; HRD+, Homologous Recombination Deficiency Positive; PFS, Progression-Free Survival; OS, Overall Survival; OC, Ovarian Cancer. This figure was created by Figdraw (https://www.figdraw.com). Abbreviations: BEV, Bevacizumab; OC, ovarian cancer; HRD, homologous recombination deficiency; PFS, progression-free survival; OS, overall survival; HR, hazard ratio; PLD, pegylated liposomal Doxorubicin. PXT, Paclitaxel. Data sources: ClinicalTrials.gov, FDA labels, and published trial results.

FIGURE 3

The factors contributing to bevacizumab resistance. (A) Hypoxia-driven malignancy: HIF-1α-mediated EMT, metabolic reprogramming, and metastasis. (B) Vessel co-option and lymphangiogenesis: Tumor cells exploit pre-existing vessels or induce lymphatic expansion. (C) Immunosuppressive TME: Infiltration of M2 macrophages and Tregs, along with stromal fibrosis. (D) Bypass angiogenesis: Activation of alternative pro-angiogenic pathways (FGF/FGFR, PDGF/PDGFR, Ang-2/Tie2). This figure was created by Figdraw (https://www.figdraw.com).

FIGURE 4

Future application strategies for Bevacizumab. (A) Immuno-angiogenic synergy (Blue): Bevacizumab synergizes with PD-1 inhibitors and vaccines to activate T cells and reprogram macrophages. (B) Targeting resistance pathways (Red): Dual inhibition of angiogenesis (Ang-2/FGFR) and hypoxia signaling to overcome adaptive resistance. (C) Innovative drug delivery systems (Purple): Nanoparticles and localized delivery enhance tumor targeting and reduce toxicity. (D) Biomarker-driven precision medicine (Orange): Dynamic biomarker monitoring and machine learning guide personalized therapy. This figure was created by Figdraw (https://www.figdraw.com).