Bevacizumab, a humanized anti-angiogenic monoclonal antibody for the treatment of colorectal cancer

Abstract

Summary Angiogenesis is the process by which new blood vessels are created from pre‐existing vessels. It is essential for the growth and development of normal cells and tissues during embryonic and neonatal development and of tumour cells. Solid tumours rely on having an extensive network of blood vessels for growth and survival. The key mediator of angiogenesis, vascular endothelial growth factor‐A (VEGF‐A), is critical for the growth of tumours and their subsequent metastasis and is known to initiate angiogenesis. Bevacizumab is a humanized immunoglobulin G monoclonal antibody that binds to VEGF with high specificity, thereby blocking VEGF‐mediated signalling pathways and thus angiogenesis. Clinical trials have shown that bevacizumab is effective in prolonging survival in patients with metastatic colorectal cancer (CRC) when combined with standard chemotherapy. Consequently, bevacizumab has been approved in combination with 5‐fluorouracil‐based chemotherapy for first‐line treatment of patients with metastatic CRC. Bevacizumab is generally well tolerated in most patients and does not exacerbate the adverse events associated with conventional chemotherapy. Bevacizumab‐related side effects are generally manageable; however, monitoring for hypertension, gastrointestinal perforation, bleeding, proteinuria and thromboembolism is advised, especially in patients with predisposing factors. In addition to demonstrated survival benefits, the convenient dosing schedule and lack of interactions should ensure the successful integration of this novel agent into clinical practice.

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

“…111 The importance of the stroma for tumor development has led to the design of therapeutic strategies aimed at targeting several cell types of the tumoral stroma, such as monoclonal antibodies devised to block the growth of MSCs as therapeutic tools and gene carriers JB Aquino et al new blood vessels. 130,131 However, a malformed vasculature and increased interstitial fluid pressure, characteristics of malignant tumors, hamper antibodies efficiencies. 132 These barriers also affect the therapeutic efficacy of viral or non-viral vectors, [133][134][135] although recent data from our group have shown that targeting stromal cells with a conditionally replicative adenoviral vector improved viral therapeutic efficacy.…”

Highly effective antiangiogenesis via magnetic mesoporous silica-based siRNA vehicle targeting the VEGF gene for orthotopic ovarian cancer therapy

“…6 Attempts have been made to treat ovarian cancer using antiangiogenesis therapy, such as bevacizumab, in the clinical setting but side effects including thrombosis, proteinuria, and gastrointestinal perforation remain problematic. [7][8][9][10][11] Therefore, it is necessary to develop safer and more effective antiangiogenesis therapies for ovarian cancer.…”

Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy

“…3 Bevacizumab (Avastin Genetech Inc., South San Francisco, California, USA) is a humanized antivascular endothelial growth factor (VEGF) antibody used for metastatic colorectal cancer. 4 Recent reports have described the application of bevacizumab to treat ocular neovascular disorders including PDR. [5][6][7][8] Adjunctive use of intravitreal bevacizumab for severe PDR before vitrectomy has also been reported, 5,6 however, the preferable timing from the injection to surgery has not been determined.…”