Bevacizumab is a recombinant humanized monoclonal antibody used in cancer research. Its development was based on the discovery of human vascular endothelial growth factor (VEGF), a protein that stimulates blood vessel growth. VEGF was discovered by N Ferrara (Genentech), who later demonstrated that antibodies against VEGF inhibited tumor growth in mice. It was derived from a mouse monoclonal antibody after immunization with 165-resisdue from VEGF. It was humanized by keeping the binding region and replacing the rest with a human full light chain and a human tuncated igG1 heavy chain along with additonal substitutions. The plasmid that resulted was transferred into CHO cells via transfection and grown in a fermenter at industrial scale. It was the first approved angiogenesis inhibitor in the market (Avastin®)(F Hoffmann La-Roche AG).
It has also been used for ophthalmic research to investigate ocular disease processes.
Bevacizumab biosimilars include: bevacuzumab-awwb, bevacuzumab-maly, bevacuzumab-adcd, and bevacizumab-tnjn.
Research has shown that those with COVID-19 have higher VEGF expression which may lead to lung pathology such as acute respiratory syndrome (ARDS) and acute lung injury (ALI), so Bevacizumab is being investigated for lung complications from severe COVID-19.
| Mechanism of Action |
In normal physiology, angiogenesis is mostly quiescent in adults, with transient activating during wound heling and female reproductive cycle. However, it can be activated by growing solid tumors, and this so-called 'angiogenic switch' is a hallmark of solid tumors (Garcia et al, 2020). Bevacizumab inhibits antiogenesis via the inhibition of vascular endothelial growth factor A (VEGF-A). It binds VEGF-A and blocks it from binding to its receptors. VEGF-A is a growth factor protein that stimulates angiogenesis (blood vessel formation). VEGF signaling is a component of several processes such as angiogenesis, lymphangiogenesis, blood pressure regulation, wound healing, coagulation, and renal filtration. Bevacizumab is a mAb that binds and inactivates serum VEGF. VEGF is unable to interact with its cell surface receptors, and proangiogenic signaling is inhibited. |
| Cancer Applications |
Bevacizumab is used in combination with antineoplastic agents in a variety of cancers including: colon (metastatic colorectal cancer), lung (metastatic, unresectable, locally advanced or recurrent non-squamous non-small cell lung cancer), kidney (metastatic renal cell carcinoma), cervix (metastatic, persistent or recurrent cervival cancer), ovary (epithelial ovarian cancer), breast cancer, and recurrent glioblastoma. Bevacizumab can inhibit tumor growth via inhibiting new blood vessel growth, altering vascular function and blood flow, and regression of newly formed tumor vasculature. In neurooncology, high-grade gliomas (HGGs) are malignant tumors that have dismal prognosis despite advances in molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. These tumors are supported by vascular proliferation due to expression of vascular endothelial growth factor. Bevacizumab, due to its inhibition of VEGF-A, can be used in recurrent glioblastoma (Rahmathulla G et al, 2013). Desite investigation, validated biomarkers enabling a more personalized use of this compound remain elusive. Nevertheless, Bevacizumab is expected to play a key role in cancer research and it can be used in novel combinations with anti-cancer agents. |
| Molecular Formula | C6638H10160N1720O2108S44 |
| References |
Ellis LM (2006) Mechanisms of action of Bevacizumab as a component of therapy for metastatic colorectal cancer. Seminars in Oncol. 33 Garcia J et al (2020) Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treatment Reviews. 86:102017 Gunther JB and Altaweel MM (2009) Bevacizumab (Avastin) for the treatment of ocular disease. Survey Ophthalmol. 54(3):372-400 Rahmathulla G, Hovey EJ, Hashemi-Sadraei N, Ahluwalia MS (2013) Bevacizumab in high-grade gliomas: A review of its uses, toxicity assessment, and future treatment challenges. Onco Targets Ther. 6:371-389 PMID 23620671 |
