Does Inflammation Stoke Cancer Growth?
Does Inflammation Stoke Cancer Growth?
Hi. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford and Past President of the European Society of Medical Oncology. I would like to talk about the tumor microenvironment. I spend a lot of time in my research lab looking at somatic tumor mutations within the cancers themselves -- particularly colorectal cancer -- that drive prognosis, the natural history of the cancer in terms of its likelihood to recur, and perhaps even predictive capacity in how the cancer will respond to drugs. I am increasingly becoming more interested in the microenvironment in which the cancer cells arise, particularly around inflammation.
We have all seen the very interesting data that are continuing to come out about aspirin -- how our cheap, good old aspirin seems to have a role in cancer prevention and how it may reduce metastasis in patients who have already developed cancer. It has yet to be proven in properly controlled prospective adjuvant trials, but inflammation is very interesting the more one looks at it. We published some data recently with some fantastic colleagues from the Netherlands showing that the stromal component of cancer, morphologically characterized, carries a huge prognostic weight. However, I think there is a big gap in our understanding about how to disentangle the elements of good and bad inflammation.
We know that a leukocyte infiltrate can be prognostically good. If it is predominantly lymphocytic and if it's the right type of lymphocyte, then that may suggest that the body is trying to mount some sort of a controlling immune response. What is much more likely, however, is that there is a proinflammatory leukocytic infiltrate. With that comes a whole host of cells that can produce cytokines that support tumor growth and angiogenesis, which may reduce the potential of the body to mount an immune response. I think we need to understand this better. There is a fantastic piece of work that remains to be done in which we, as clinicians, can support our colleagues in the fundamental and basic laboratories where we start to perturb the inflammatory system, not just with the blunderbuss approach of aspirin or COX [cyclooxygenase]2 inhibitors, but by taking out interleukin-6 (IL-6), IL-17, IL-23, or whatever our colleagues think the relevant cytokines might be. By doing this in the human disease setting, we can understand more of the mechanisms of inflammation and how we might intervene.
For example, many of these cytokines activate the JAK-STAT signaling pathway and the NF-kappaB pathway in cancer cells. Are these legitimate drug targets? Should we be exploring these pathways for the development of new agents? There is much to be learned. I guess I am challenging those of you who are listening to see how we can bring the clinical and basic communities together to address this extraordinary topic. Thanks for listening. As always, I would be very pleased to take any comments or anything that you might have to add to my warble. Thank you.
Hi. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford and Past President of the European Society of Medical Oncology. I would like to talk about the tumor microenvironment. I spend a lot of time in my research lab looking at somatic tumor mutations within the cancers themselves -- particularly colorectal cancer -- that drive prognosis, the natural history of the cancer in terms of its likelihood to recur, and perhaps even predictive capacity in how the cancer will respond to drugs. I am increasingly becoming more interested in the microenvironment in which the cancer cells arise, particularly around inflammation.
We have all seen the very interesting data that are continuing to come out about aspirin -- how our cheap, good old aspirin seems to have a role in cancer prevention and how it may reduce metastasis in patients who have already developed cancer. It has yet to be proven in properly controlled prospective adjuvant trials, but inflammation is very interesting the more one looks at it. We published some data recently with some fantastic colleagues from the Netherlands showing that the stromal component of cancer, morphologically characterized, carries a huge prognostic weight. However, I think there is a big gap in our understanding about how to disentangle the elements of good and bad inflammation.
We know that a leukocyte infiltrate can be prognostically good. If it is predominantly lymphocytic and if it's the right type of lymphocyte, then that may suggest that the body is trying to mount some sort of a controlling immune response. What is much more likely, however, is that there is a proinflammatory leukocytic infiltrate. With that comes a whole host of cells that can produce cytokines that support tumor growth and angiogenesis, which may reduce the potential of the body to mount an immune response. I think we need to understand this better. There is a fantastic piece of work that remains to be done in which we, as clinicians, can support our colleagues in the fundamental and basic laboratories where we start to perturb the inflammatory system, not just with the blunderbuss approach of aspirin or COX [cyclooxygenase]2 inhibitors, but by taking out interleukin-6 (IL-6), IL-17, IL-23, or whatever our colleagues think the relevant cytokines might be. By doing this in the human disease setting, we can understand more of the mechanisms of inflammation and how we might intervene.
For example, many of these cytokines activate the JAK-STAT signaling pathway and the NF-kappaB pathway in cancer cells. Are these legitimate drug targets? Should we be exploring these pathways for the development of new agents? There is much to be learned. I guess I am challenging those of you who are listening to see how we can bring the clinical and basic communities together to address this extraordinary topic. Thanks for listening. As always, I would be very pleased to take any comments or anything that you might have to add to my warble. Thank you.
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