Search Videos by Topic or Participant
Browse by Series:

Dysregulated Angiogenesis in Lung Cancer

Insights From: Joachim G. Aerts, MD, PhD, Erasmus Medical Center Cancer Institute; Enriqueta Felip, MD, PhD, Vall d’Hebron University Hospital; Marina Garassino, MD, National Cancer Institute of Milan; Roy Herbst, MD, Yale School of Medicine
Published: Friday, Nov 11, 2016


Transcript:

Marina Garassino, MD:
Angiogenesis is a long story in non–small cell lung cancer. We know that it’s been a very important hallmark since the 70s, from the first studies of Judah Folkman, and it became a very important target for treating patients with advanced non–small cell lung cancer at the end of the 90s. And, in the next decade, we had several studies targeting the angiogenesis. This is because angiogenesis is expressed in more than 40% to 70% of lung tumors, and we also know that patients expressing, for example, VEGF, have a worse prognosis than patients without. We know that all the signals of angiogenesis are promoting the tumor growth, proliferation, and the creation of microvessels, thereby creating the phenomenon of metastasization.

We have several receptors, and the most important receptor is the vascular endothelial growth factor (VEGF) receptor. The vascular endothelial growth factor can be at least in three isoforms. We also have several ligands called VEGF-A, B, C, and D. We also have the fifth, the placenta growth factor (PIGF), which is another growth factor. Then, we have all the downstream. The downstream is very important to promote the creation of vessels, and this is one of the most important mechanisms for non–small cell lung cancer.

Enriqueta Felip, MD, PhD: Angiogenesis is a hallmark of cancer. When the tumor is growing, a number of ligands stimulating angiogenesis are secreted by the tumor. This will stimulate the endothelial cells, and this is crucial for the formation of new vessels. The reality is, the tumor depends on the formation of these new vessels to grow. So, this process is key in proliferation and also in the metastases. It is a clear rationale to inhibit this process, to inhibit the angiogenesis, and this could be a good strategy in all tumors when we treat a cancer patient.

Joachim G. Aerts, MD, PhD: Tumor angiogenesis also has a lot of effects on the immunosuppression. One of the things is that the tumor angiogenesis is also based on immune cells. So, the tumor secretes all kinds of cytokines which cause immune cells to also become endothelial cells. And one of the difficult points is when we reduce the angiogenesis, whether the tumor becomes hypoxic. You could probably also imagine that the immune system will work less. That’s why, on the other hand, when we use these antiangiogenic agents, we see that the perfusion of tumors is becoming better. Probably then there will be more oxygen, more nutrients, so the immune system can work even better. It’s quite a difficult field, [so] that we don’t know yet what the balance between the two is.

On the one hand, we have these tumor vessels. The vessels in the tumor can probably increase the immune activity. And on the other hand, the mechanism on how these immunosuppressive cells occur in the tumor is also dependent on the cytokines released by the tumor. So, it’s on the two-edge sword in which we don’t know what the balance is yet.

Transcript Edited for Clarity
Slider Left
Slider Right


Transcript:

Marina Garassino, MD:
Angiogenesis is a long story in non–small cell lung cancer. We know that it’s been a very important hallmark since the 70s, from the first studies of Judah Folkman, and it became a very important target for treating patients with advanced non–small cell lung cancer at the end of the 90s. And, in the next decade, we had several studies targeting the angiogenesis. This is because angiogenesis is expressed in more than 40% to 70% of lung tumors, and we also know that patients expressing, for example, VEGF, have a worse prognosis than patients without. We know that all the signals of angiogenesis are promoting the tumor growth, proliferation, and the creation of microvessels, thereby creating the phenomenon of metastasization.

We have several receptors, and the most important receptor is the vascular endothelial growth factor (VEGF) receptor. The vascular endothelial growth factor can be at least in three isoforms. We also have several ligands called VEGF-A, B, C, and D. We also have the fifth, the placenta growth factor (PIGF), which is another growth factor. Then, we have all the downstream. The downstream is very important to promote the creation of vessels, and this is one of the most important mechanisms for non–small cell lung cancer.

Enriqueta Felip, MD, PhD: Angiogenesis is a hallmark of cancer. When the tumor is growing, a number of ligands stimulating angiogenesis are secreted by the tumor. This will stimulate the endothelial cells, and this is crucial for the formation of new vessels. The reality is, the tumor depends on the formation of these new vessels to grow. So, this process is key in proliferation and also in the metastases. It is a clear rationale to inhibit this process, to inhibit the angiogenesis, and this could be a good strategy in all tumors when we treat a cancer patient.

Joachim G. Aerts, MD, PhD: Tumor angiogenesis also has a lot of effects on the immunosuppression. One of the things is that the tumor angiogenesis is also based on immune cells. So, the tumor secretes all kinds of cytokines which cause immune cells to also become endothelial cells. And one of the difficult points is when we reduce the angiogenesis, whether the tumor becomes hypoxic. You could probably also imagine that the immune system will work less. That’s why, on the other hand, when we use these antiangiogenic agents, we see that the perfusion of tumors is becoming better. Probably then there will be more oxygen, more nutrients, so the immune system can work even better. It’s quite a difficult field, [so] that we don’t know yet what the balance between the two is.

On the one hand, we have these tumor vessels. The vessels in the tumor can probably increase the immune activity. And on the other hand, the mechanism on how these immunosuppressive cells occur in the tumor is also dependent on the cytokines released by the tumor. So, it’s on the two-edge sword in which we don’t know what the balance is yet.

Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Cancer Summaries and Commentaries™: Update from Chicago: Advances in the Treatment of Breast CancerJul 31, 20181.0
Community Practice Connections™: The Next Generation in Renal Cell Carcinoma Treatment: An Oncology Nursing Essentials WorkshopJul 31, 20181.5
Publication Bottom Border
Border Publication
x