2004: Bevacizumab: First Anti-Angiogenic Cancer Drug (2004)
Bevacizumab (Avastin), approved by the FDA in February 2004 for metastatic colorectal cancer,
became the first anti-angiogenic therapy approved for any solid tumour, validating a strategy
that had been hotly debated for three decades. The scientific foundation traced to Judah Folkman
at Boston Children's Hospital, who proposed in 1971 that tumours require neovascularisation to
grow beyond 1–2 mm and that blocking tumour-induced angiogenesis could therefore arrest tumour
growth—a hypothesis that met with widespread scepticism for over two decades.
The key molecular target emerged in 1989 when Napoleone Ferrara at Genentech identified and
cloned vascular endothelial growth factor (VEGF), a secreted glycoprotein that potently promotes
endothelial proliferation and vascular permeability. Genentech's antibody programme against VEGF
produced bevacizumab, a humanised monoclonal that neutralises all biologically active isoforms of
VEGF-A, preventing receptor binding and thereby suppressing tumour-associated angiogenesis. In
xenograft models, bevacizumab consistently reduced tumour vascularity and—when combined with
chemotherapy—produced synergistic antitumour activity.
The pivotal Phase III trial in metastatic colorectal cancer showed that adding bevacizumab to
standard irinotecan/fluorouracil/leucovorin chemotherapy extended median overall survival from
15.6 to 20.3 months, a 30 % improvement. The FDA granted accelerated approval in February 2004,
marking the commercial birth of the anti-VEGF drug class. Bevacizumab subsequently received
approvals across multiple indications including non-small-cell lung cancer, metastatic breast
cancer (later withdrawn), glioblastoma, renal cell carcinoma, and ovarian cancer.
The drug also demonstrated an unexpected ophthalmological application: intraocular injection of
bevacizumab is now widely used off-label in neovascular age-related macular degeneration, where
VEGF-driven choroidal neovascularisation can be suppressed to preserve vision.
Tại sao điều này quan trọng
Bevacizumab validated Judah Folkman's angiogenesis hypothesis after three decades of controversy
and launched the anti-VEGF drug class. It established tumour vasculature as a legitimate
therapeutic target, showed that non-cancer-cell-directed therapy could meaningfully extend
survival, and pioneered combination biologics-plus-chemotherapy regimens that have since become
the backbone of multiple solid tumour treatment protocols.