CancerNetwork: You are giving a talk at the upcoming pancreatic cancer American Association of Cancer Research conference on a cancer stem cell approach for pancreatic cancer. Are there specific pancreatic cancer stem cell markers that are currently in development?
Dr. Simeone: There certainly are. Our laboratory did the initial work in identifying cancer stem cells within human pancreatic cancers. What that means is that there is a small subset of cancer cells within a cancer that are stem cell–like that are more primitive and seem to be the drivers of the development of pancreatic cancer and importantly, we think, in the development of metastases. We have described cell surface markers that define what cancer stem cells are, and we are continuing to refine what those markers are as we move forward. Importantly, what we would like to do is beyond knowing what the cell-surface markers are, but understanding the key signaling pathways that regulate the function of cancer stem cells because we know from our work, that these cancer stem cells are quite resistant to chemotherapy and radiation. So we think understanding these cells in a deeper way will allow us to develop targeted therapies to eradicate these cancer stem cells from the tumor which we think will be an important part of a cancer cure.
CancerNetwork: Do you see the cancer stem cell approach more as way to identify therapeutic targets and maybe not so much in terms of a diagnostic tool?
Dr. Simeone: Well, I think the diagnostic piece is still a question mark. I think that remains to be seen. But, certainly, from a therapeutic standpoint, it seems to be an important piece of the puzzle.
CancerNetwork: Do some of the characteristics of pancreatic cancer stem cells, do they overlap with the characteristics that have been identified for breast cancer stem cells, for example, and other tumor types?
Dr. Simeone: It is interesting. There is definitely some overlap with cancer stem cells in other cancer types. But there are also significant differences. And so there is a lot of talk of, “If we understand signaling pathways in one cancer, it will be relevant across all other cancers.” I actually don’t think that that is necessarily true. Significant inroads have been made into treating other cancers that have not happened for pancreatic cancer, and I think pancreatic cancer is its own unique entity, and we need to study it as an individual cancer. This doesn’t mean that we can’t learn from other cancers, but I think to really understand how to treat pancreatic cancer, we will have to study the disease specifically.
CancerNetwork: Could you describe what the major treatment options are now for advanced pancreatic adenocarcinomas?
Dr. Simeone: So the main treatment options now for advanced pancreatic cancer are combination chemotherapy and the standard backbone of chemotherapy for advanced pancreatic cancer has traditionally been a drug called gemcitabine (Gemzar). That has had some benefit to patients, although there are newer regimens that seem to have a higher level of efficacy. In particular, a regimen called FOLFIRINOX. The trade-off there is that the side effect profile is much more significant so patients have a much harder time tolerating that regimen. There are also a lot of other promising treatments that are being tested both in laboratories, in preclinical model systems and also in very early phase clinical trials that I think hold promise. I suspect in the next few years we will have a good understanding of a number of these new approaches and what role they will play in treating pancreatic cancer. But, importantly, I think we are now having more people in the field and really trying to drill down and understanding how pancreatic cancer works and how we might best treat it.
CancerNetwork: Two new treatments were approved last year, specifically for pancreatic neuroendocrine tumors. One is sunitinib (Sutent), which is a receptor tyrosine kinase and also everolimus (Afinitor), an mTOR inhibitor. How do you put this in the context of pancreatic neuroendocrine treatments and do you see these as major advances?
Dr. Simeone: So I think these are advances. Anytime we can take an advanced disease and have some impact on improving progression-free survival, that is definitely an advance. And both of these agents were found to significantly improve progression-free survival in phase III, randomized trials. However, one of the issues with neuroendocrine tumors is that some of the tumors are very indolent and others are much more biologically aggressive, and we don’t have a good understanding currently of which tumors are the more aggressive ones. And even though these treatments have provided advances, they haven’t really resulted in cures. I think it moves things one step closer to where we want to be, but I still think that we have a long way to go.
CancerNetwork: Thank you so much for joining us, Dr. Simeone.
Dr. Simeone: You’re welcome, thank you.