It has been found that inhibition of the VEGF-A pathway may be a promising new antitumor strategy. By inhibiting the ligand, VEGF-A is not able to bind or interact with any of its receptors, VEGFR-1, VEGFR-2 or neuropilin-1. While inhibition of any of these receptors may cause a wider range of inhibitory effects beyond the VEGF-A pathway, inhibiting VEGF-A only inhibits the VEGF-A pathway, decreasing possible complications. This concept of targeting the VEGF-A ligand in order to inhibit tumor growth and metastasis is the basis of the new treatment Bevacizumab. Bevacizumab uses a humanized monoclonal antibody designed to target VEGF-A, and has been shown to prolong the life of patients with metastatic lung and breast cancers. Unfortunately the cost of producing Bevacizumab is extremely high, making the treatment cost $100,000 a year. If another cheaper method were found for inhibiting the VEGF-A pathway it would be groundbreaking. RNA ligands called aptamers can be used to inhibit protein function, binding with high specificity and affinity, and are cheaper, more efficient replacements for antibodies.
The selection of RNA aptamers against VEGF-A could be the first step in finding an RNA ligand that could inhibit the VEGF-A pathway, slowing the growth of tumors and preventing metastasis. If the nucleotide sequence was shared as part of the People’s Aptamer Project, then drug companies could develop a cheaper, more effective, replacement to the already existing drug Bevacizumab.
Figure 1: The interaction of the VEGF-A ligand with VEGFR-1, VEGFR-2 and nueropilin-1 lead to the development of vasculature which helps tumor development and can lead to metastasis.
1. Hicklin DJ, Ellis LM. J Clinical Oncology. 2005;23:1011-1027.
2. Presta LG, Chen H, O’Connor SJ, et al. Cancer Res. 1997;57:4593-4599.