Angiogenesis, the generation of new blood vessels, is an essential physiological process that can be dysregulated in various pathological conditions, including cancer. The vascular endothelial growth factor (VEGF) pathway is considered the most important and is a well-characterized contributor to angiogenesis. VEGF-A and other members of the VEGF family such as placental growth factor (PlGF) are upregulated in pathological conditions. VEGF-A, the first VEGF characterized, has served as a paradigm for the development of antiangiogenesis as a therapeutic strategy.
Till now, the research of anti-VEGF on breast cancer has not yet succeeded except for the three initial trials.The US Food and Drug Administration approved ramucirumab for use in gastric cancer, where it (albeit modestly) improves both PFS and overall survival. However, VEGF-based therapy for breast cancer has gone through failures and failures.Since ramucirumab, like bevacizumab and sunitunib, target essentially the same process (VEGF-driven angiogenesis) in the same disease, its failure is perhaps unsurprising, just like what has happened in bevacizumab and sunitunib.
Given that angiogenesis is an established hallmark of progressively detrimental tumors, including Lung cancer, inhibiting proangiogenic factors represents a potential avenue for therapeutic development. While the role of VEGF in angiogenesis is well-established, it is also known that additional signaling molecules and pathways contribute to aberrant blood vessel formation. Notably, some studies postulate that inhibiting VEGF and its receptors (VEGFRs) in early treatment settings may be beneficial, but that prolonged exposure to VEGF/VEGFR inhibitors may allow tumor cells to utilize alternative mechanisms to find oxygen and nutrients to sustain their growth.
Traditionally, androgen ablation has been the main treatment for the prevention of metastases from prostate cancer. As prostate cancer cells are initially dependant on androgens, suppressing the levels of testosterone and dihydrotestosterone decreases the growth rate of prostate cancer cells. However, after this initial response these cells can become castrate-resistant and develop a more aggressive phenotype, with increased VEGF expression and proliferative potential.
Due to the multifaceted effect VEGF has on tumour angiogenesis and tumour cell proliferation, antiangiogenic therapies targeting the VEGF pathways have shown promising early clinical application and are being investigated in clinical trials. These anti-VEGF therapies consist of VEGF-neutralizing antibodies and tyrosine kinase receptor inhibitors.
Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF)-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States), VEGF receptors (eg, ramucirumab), and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors) for Colorectal Cancer