© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Introduction: In colorectal cancer, anti-VEGF agents have demonstrated a survival benefit when combined with chemotherapy. However, development of resistance is very common. One of the mechanisms is due not to a failure in the VEGFR blockade, but rather to development of compensatory mechanisms of resistance, such as hypoxia-triggered upregulation of other proangiogenic factors, like placental growth factor (PlGF). Areas covered: This article summarizes the fundamental role of PlGF in the development of resistance to antiangiogenic treatment as well as the efficacy of aflibercept, ramucirumab, and regorafenib. Expert opinion: Aflibercept functions as a soluble decoy receptor precluding VEGFs and PlGF from binding to native VEGFR, and therefore preventing the emergence of resistance. Bevacizumab limits its function to preventing the interaction between VEGF-A and VEGFR. In combination with FOLFIRI (VELOUR trial), aflibercept improves survival in patients with metastatic CRC who are resistant or have progressed to oxaliplatin-based chemotherapy. Ramucirumab, a fully humanized immunoglobulin G1 (IgG-1) monoclonal antibody and regorafenib, a multikinase inhibitor, have significant improvement for overall survival as well as for progression-free survival in chemotherapy refractory settings.
- Colorectal cancer
- placental growth factor
- resistance to antiangiogenic treatment
Macarulla, T., Montagut, C., Sánchez-Martin, F. J., Granja, M., Verdaguer, H., Sastre, J., & Tabernero, J. (2019). The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls. Expert Opinion on Biological Therapy. https://doi.org/10.1080/14712598.2020.1677603