bevacizumab

Overview

Bevacizumab (trade name Avastin; Wikidata: Q413299) is a recombinant humanized monoclonal IgG1 antibody that targets vascular endothelial growth factor A (VEGFA), a key driver of tumor angiogenesis. By binding VEGFA with high affinity, bevacizumab prevents it from coupling with its cognate receptors (VEGFR-1/FLT1 and VEGFR-2/KDR), thereby disrupting the angiogenesis signaling pathway and starving tumors of the new blood vessel formation required for growth and metastasis. Its mechanism is distinct from small-molecule tyrosine kinase inhibitors such as sorafenib or lenvatinib in that it acts extracellularly and with high target specificity. Since receiving initial FDA approval in 2004, bevacizumab has become one of the most widely deployed anti-angiogenic agents in oncology, with established indications spanning colorectal cancer, non-small cell lung cancer, glioblastoma, renal cell carcinoma, and cervical cancer, among others.

Beyond its canonical anti-angiogenic role, bevacizumab has demonstrated pleiotropic effects on the tumor microenvironment. Inhibition of VEGFA signaling can normalize tumor vasculature, potentially improving drug delivery and immune cell infiltration. In combination with immune checkpoint inhibitors such as atezolizumab, this vascular normalization is hypothesized to enhance antitumor immunity by reducing immunosuppressive growth factors (including TGF-β1 and VEGF) and enabling more effective cancer immunotherapy. Its pharmacokinetics—including behavior in the injected eye compartment, systemic circulation, and the contralateral fellow eye—continue to be studied across both oncologic and ophthalmic settings.

Focus of Latest Publications

Recent publications extensively examined atezolizumab plus bevacizumab as first-line immunotherapy for unresectable hepatocellular carcinoma, documenting real-world diagnostic pathways, response patterns using RECIST and modified RECIST criteria, optimal dosing strategies, and clinical factors predicting long-term survival. Sequential therapy following first-line progression was compared across alternative approaches including lenvatinib and durvalumab plus tremelimumab, with analyses characterizing treatment selection patterns and outcomes from prospective cohorts. Bevacizumab-containing regimens demonstrated durable benefit in patients undergoing liver transplantation following immunotherapy, despite tumor burden exceeding conventional candidacy criteria. For patients with HCC refractory to atezolizumab plus bevacizumab, balloon-occluded transarterial chemoembolization was investigated as a salvage approach. Cost-effectiveness analyses across multiple healthcare systems supported atezolizumab plus bevacizumab as a value-bearing first-line option.

Beyond HCC, bevacizumab was integrated into multidrug regimens across diverse solid tumors. Phase III trials demonstrated sustained efficacy of atezolizumab with carboplatin and pemetrexed plus or without bevacizumab in advanced non-small cell lung cancer, while in triple-negative breast cancer, bevacizumab plus paclitaxel was evaluated as induction therapy preceding immunotherapy. Mechanistic investigations revealed that bevacizumab induces apoptosis in glioblastoma through upregulation of microRNA-4695-5p and suppression of PKMYT1. Clinical evaluation extended to colorectal cancer (including combinations with trifluridine-tipiracil), neuroblastoma (with irinotecan and temozolomide), recurrent cervical cancer, ovarian cancer (as rechallenge with PARP inhibitors), small bowel adenocarcinoma, and alveolar soft part sarcoma. Real-world analyses characterized bevacizumab-associated adverse events, including delayed wound healing around central venous ports and increased risk of port-related vein stenosis in colorectal cancer patients.

Studies of acquired bevacizumab resistance in ovarian cancer identified enolase 1 (ENO1) lactylation as a key driver of drug resistance through metabolic reprogramming and enhanced angiogenesis; lactate-mediated post-translational modifications of ENO1 upregulated endothelial-specific molecule 1 (ESM1), establishing a positive feedback loop that promoted endothelial cell survival. In clear cell renal cell carcinoma, comprehensive multi-omics analysis identified FLT1-mediated crosstalk between epithelial and endothelial cells as central to disease progression, with evidence supporting combination therapy of bevacizumab with FLT1 and AKT inhibitors for patients with high-FLT1 tumors. These mechanistic insights provided rationale for rational combination strategies and identification of biomarkers to predict bevacizumab response.

Analytical and formulation studies advanced bevacizumab characterization and delivery. Dynamic light scattering methods established models for assessing protein oligomerization in therapeutic formulations, while single-molecule oscillator approaches simultaneously measured size and charge at single-protein resolution. Mass spectrometry peptide mapping defined amino acid sequence and post-translational modifications with enhanced coverage using complementary proteases. A novel insulin-like growth factor II-based masking domain was engineered to enable protease-dependent conditional activation of bevacizumab, potentially improving safety by restricting systemic target engagement. Pharmacokinetic modeling of intravitreally administered bevacizumab characterized blood-ocular barrier dynamics and retinal penetration, while multistage drug delivery systems were developed for sustained co-delivery of bevacizumab with irinotecan in colorectal cancer. Microfluidic tumor-angiogenesis models enabled real-time assessment of bevacizumab efficacy against patient-derived tumoral and endothelial interactions.

Key Publications

• NEWJul Balloon-occluded Alternative Infusion of Fragmented Gelatin Particles of TACE for Hepatocellular Carcinoma Refractory to Atezolizumab-Bevacizumab. (Anticancer research, 2026, PMID 42373279): "This study aimed to verify the efficacy and safety of balloon-occluded alternative infusion of cisplatin solution and gelatin particles of transarterial chemoembolization (BOAI-TACE) for hepatocellular carcinoma (HCC) refractory or intolerant to atezolizumab plus bevacizumab combination therapy."
• NEWJun Simple Hydrodynamic Molecular Weight Model for Rapid Assessment of Therapeutic Protein Oligomerization States in Formulation. (The AAPS journal, 2026, PMID 42373916): "The resulting MWhd values were several-fold greater than the corresponding monomeric MW of the glucagon-like peptide-1/2 (GLP-1/2) analogs, insulin analogs, and the monoclonal antibodies (mAbs) infliximab and bevacizumab, indicating varying degrees of oligomerization."
• NEWJun Second-Line Practices in the Era of Immunotherapy in HCC: The CHIEF Cohort. (JHEP reports : innovation in hepatology, 2026, PMID 42276189): "This study aimed to describe access to and outcomes of second-line (2L) treatments following atezolizumab-bevacizumab (AB) compared with sorafenib (Sor),"
• May Diagnostic Pathways and Outcomes of First-Line Atezolizumab plus Bevacizumab in Patients with Locoregional Therapy-Ineligible Hepatocellular Carcinoma at Initial Diagnosis. (Oncology, 2026, PMID 42213615): "We examined diagnostic pathways and outcomes of first-line atezolizumab plus bevacizumab (Atz+Bev), with a focus on de novo LRT-ineligible HCC."
• Jun Bevacizumab for Radiation-Induced (Radiculo)plexopathy. (European journal of neurology, 2026, PMID 42206990): "The objective of this work was to evaluate the effectiveness of the anti-VEGF bevacizumab in the treatment of RI(R)P."
• May Ameliorative effects of bevacizumab against sepsis-induced acute kidney injury: investigation of inflammatory responses, pyroptosis-related signalling and angiogenesis in a murine model of polymicrobial sepsis. (Molecular biology reports, 2026, PMID 42201618): "Bevacizumab is a biopharmaceutical agent that disrupts the angiogenesis signalling pathway by binding to vascular endothelial growth factor (VEGF) and preventing it from coupling with cognate receptors."
• May Chemoport-related right innominate vein stenosis in patients with colorectal cancer: A retrospective risk factor analysis. (PloS one, 2026, PMID 42160312): "In the 728 palliative patients, bevacizumab treatment was significantly associated with a higher risk of CR-RIVS (hazard ratio=1.51, 95% confidence interval: 1.25-1.82, P<0.001), whereas cetuximab was not (p=0.85)."
• Jun Liver Transplantation After Immune Checkpoint Inhibition in Hepatocellular Carcinoma-Data From the Multinational LITCHI Registry. (Liver international : official journal of the International Association for the Study of the Liver, 2026, PMID 42156355): "Among 18 patients who underwent LTx following ICI, 15 were treated with atezolizumab plus bevacizumab."
• May Economic evaluation of finotonlimab plus bevacizumab as first-line therapy for advanced hepatocellular carcinoma. (PloS one, 2026, PMID 42133639): "To compare the cost-effectiveness of dual-agent group (finotonlimab combined with a bevacizumab biosimilar) (SCT510) versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HCC) from the perspective of the Chinese healthcare system."
• May Bevacizumab induces apoptosis in glioblastoma cells by upregulating miR-4695-5p to inhibit PKMYT1. (RNA biology, 2026, PMID 42133791): "We sought to determine the pro-apoptotic effects of bevacizumab in glioblastoma (GBM) and to elucidate the contribution of the miR-4695-5p/PKMYT1 pathway to this process."