The discovery of Bevacizumab. An historical reappraisal.

In 1997, the monoclonal antibody A4.6.1 was humanized to create Bevacizumab (Avastin, Genentech), an antibody suitable for clinical trials. In February 2004, Bevacizumab was approved in a randomized double-blind phase III study in which was administered in combination with bolus IFL (irinotecan, 5FU, leucovorin) chemotherapy as first-line therapy for previous untreated metastatic colorectal cancer. In 2020, the EMA approved the first biosimilar of Bevacizumab for the treatment of multiple types of cancer. The administration of Bevacizumab became popular among ophthalmologists for different ocular diseases. However, in most cases of cancers, including breast, melanoma, pancreatic and prostate cancer, Bevacizumab failed to increase survival. Despite impressive performances in animal models, however, inhibitors are not performing nearly as well in humans. The limitations of applying Bevacizumab are attributed to drug resistance, metastasis promotion and reduced delivery of chemotherapeutic agents, resulting from the dramatic decrease in tumor vasculature.