Targeting Angiogenesis in Non–Small Cell Lung Cancer

Transcript:Joachim G. Aerts, MD, PhD: One of the interesting things about antiangiogenic agents is the fact that they increase tumor blood flow. On the one hand, we always think that antiangiogenic agents will decrease blood flow—but they increase blood flow. So, the tumors are more exposed to oxygen, nutrients, and immune cells. And an increase in tumor oxygen will ultimately cause, for instance, the immune system to become more effective. Tumors, to an extent, do better when they are hypoxic. We increase the blood flow in the tumor via antiangiogenic agents, and that’s going to have a beneficial effect on the immune cells, but also on the delivery of chemotherapy. Radiotherapy will work better when tumors are having a higher oxygen level.

Marina Garassino, MD: VEGF is the most important target for angiogenesis, and we can target VEGF through at least the three mechanisms. The first one is targeting the ligands, and we know that we have five ligands: VEGF-A, B, C, D, and the PIGF. Then, we can target the receptor. We have a family of receptors, which are the 1, 2, and 3. The second is the most important receptor for the pathogenesis of lung cancer. We can also use tyrosine kinase inhibitors targeting the downstream of the receptor. Now we have at least three possibilities to target in the angiogenesis.

So, we have at least two strategies to target with monoclonal antibodies. One strategy is consistent targeting of the ligand, mainly the ligand A, and the most famous drug and approved drug for the treatment of non—small cell lung cancer is bevacizumab. Then, we can also target the receptor. This is the case of the VEGF receptor 2, and this is the case of ramucirumab.

Enriqueta Felip, MD, PhD: The anti-VEGFR TKIs are inhibiting the intracellular domain of the vascular endothelial growth factors. The most important is the vascular endothelial growth factor receptor 2, but there are a number of them, and this is the way they are inhibiting this intracellular domain of the receptor. Bevacizumab is acting in a different way. Bevacizumab is inhibiting the vascular endothelial growth factor, so it is inhibiting the ligand.

Transcript Edited for Clarity