Heinz-Josef Lenz, MD: Updates on Various Gastrointestinal Cancers at ASCO 2011

Heinz-Josef Lenz, M.D., FACP, is the Associate Director for Clinical Research and Co-Leader of the Gastrointestinal Cancers Program at the USC Norris Comprehensive Cancer Center. He sat with The Group Room at ASCO 2011 to discuss updates on various gastrointestinal cancers including esophageal cancer, GIST (gastrointestinal stromal tumors) and pancreatic cancer.

The Group Room at the 2011 American Association For Cancer Research Annual Meeting was made possible, in part, by:

 

VIDEO TRANSCRIPT

Selma R. Schimmel, Founder & CEO, Vital Options International:

This is Selma Schimmel at ASCO 2011 in Chicago where our discussion continues with some of the most noted oncologists and key opinion leaders reporting on different areas of cancer, all cancer types here at the ASCO meeting. And now we’re with one of our Group Room regulars and favorites. In fact he is our GI cancer key opinion leader, Doctor-Professor Heinz-Josef Lenz, Associate Director for Clinical Research and Co-Leader of the Gastrointestinal Cancer’s Program at the USC Norris Comprehensive Cancer Center, Professor of Medicine and Preventive Medicine at the Keck School of Medicine at the University of Southern California in Los Angeles. I want to ask you about pancreatic cancer, anything happening in that arena?

Heinz-Josef Lenz, MD, Scientific Director, USC/Norris Cancer Genetics Unit:

Not so much. I think we are learning to accept that when we get new drugs such Cetuximab, Bevacizumab in clinical trials did not actually meet our expectations. We were hoping that these new target drugs would change outcome. I think it forces us to go back on the drawing board, and maybe to understand and really classify pancreatic cancer in a completely new way with the new technologies developing because that at the moment is our biggest hope for success – to understand what potential pathways are driving pancreatic cancer. Do we have to rethink potential new approaches? There are some promising new drugs being developed for pancreatic cancer but we are not even close that this comes on the market. This one clinical trial in particular important which is the side of combination because that’s showed significant promise in phase two, so we will have to wait for this. But for the other drugs which actually target not only the tumor but the macro-environment, I think they have some potential benefit because pancreatic cancer is a very unique cancer which interferes with the long environment for its inflammatory response, and there are now new drugs which interfere with that process. And I think that is probably a more promising approach in order to deal with this very difficult cancer.

Selma R. Schimmel:

Esophageal cancer, another difficult GI cancer, these patients have to go through quite a lot – surgery, radiation, chemotherapy… And, what about the integration of the targeted therapies?

Heinz-Josef Lenz:

So the GI junctions, or the space between the esophagus and the stomach is the fastest growing cancer in the western world.

Selma R. Schimmel:

Why?

Heinz-Josef Lenz:

So, there are a lot of speculations. One of them is that the use of antacids. So a lot of patients have reflux, mainly based on their diet and when you stop the acid production you may have more build-away reflux. Now bile is not an easy substance, it’s actually a carcinogen. So it can actually infuse on-going inflammatory changes in the mucosa eventually go into cancer.

Selma R. Schimmel:

Like erosion?

Heinz-Josef Lenz:

So they have rows of gastritis, they have Barrett’s esophagus, and eventually it can develop into cancer. That’s one of the hypothesis.

Selma R. Schimmel:

So you raise a very important point on the prevention or warning sign level, which is if a patient is having to take more and more antacids you need to get to the root of the problem and not just assume after continued use that this is just simple heartburn.

Heinz-Josef Lenz:

Yes, I think there is on-going discussions as you know, in certain ethnicities, like in Japan gastric cancer is being screened, not colon. Now they’re changing it for colon because of increase in colon cancer. In this country we may have in the future to be developing better screening guidelines for gastro esophageal cancer. But I think one of the symptoms when you have on-going reflux symptoms or heartburn, which is not controlled or requires on-going treatment with this over-the-counter medication, you need to have an evaluation with the gastroenterologist. I think there is no doubt about that.

Selma R. Schimmel:

One of the cancers being presented here data-wise is GIST. Most people don’t know what GIST is.

Heinz-Josef Lenz:

So GIST is a very unique tumor, a very rare tumor. It’s called GastroIntestinal Stromal Tumor. It’s actually not a cancer, it’s a sarcoma, it comes from cells which are not epithelium cells. The most common sign for GIST is the stomach. That’s the reason GI oncologists seems to see these patients and treat it. Now, there is something very unique about these tumors because they have one fighting mutation, one major intersection, not two, not three, not four. One, and this intersection is called c-kit. That’s the mutation which makes this tumor develop, grow, and at the same time sensitive to treatment. Because we have a drug called Imatinib or Gleevec, which inhibits exactly this intersection. GIST is the example of what we’re talking about.

Selma R. Schimmel:

And, if I recall, Gleevec made news several years ago for blood cancer.

Heinz-Josef Lenz:

CML, because it has also in fact on another onco-gene found in CML. So after that, now that is an example I use always on my students and for my residents and fellows, with this drug – because these tumors basically all have this mutation – the success rate is 80, 90 percent.

Selma R. Schimmel:

Amazing.

Heinz-Josef Lenz:

So they have the mutation, they take the drug, story finished. It’s not. Now we know that the mutation, depending on the site of this particular gene – X-09 or X-11 – makes a big difference. Prognosis is different, the sensitivity is different. So for X-09 mutation we give double dose. So that is where it’s biology 101. To know the mutation is not good enough, you need to know the characteristic of the mutation. Because depending where this genetic change is in this gene the function of the gene may be more or less. So you need more or less drug, and we even know how this gene responds to this treatment by generating additional mutation under the treatment where we have additional treatment developed. So GIST is a wonderful example because it makes it easier because you have one particular gene. There are others now being developed, but less frequent. A wonderful example for modern drug development and molecular biology of particular cancers and tumors.

Selma R. Schimmel:

One other GI cancer, liver cancer.

Heinz-Josef Lenz:

Yes. So liver cancer will be a challenge for our country in the future because we will not have seen the tip of the development of HCC because of the infection with Hep-B and Hep-C. I think what we have learned over the years is that Hepatitis B or Hepatitis C induced cancers are different. We know that HCC developed in Asia and the US are different.

Selma R. Schimmel:

Are the differences environmental? Is it what we ingest? Food? Preparation?

Heinz-Josef Lenz:

I think, certainly how this disease developed but just then you have a different virus used in cancer if it’s Hep-B or Hep-C it will be a different kind of cancer. It will respond differently, it will have a different prognosis. Some will change dramatically the normal liver into a fat project or a symbiotic liver, and others don’t. Now everybody has very easy time to diagnose HCC in the liver because it’s characterized. It’s typical. You don’t need pathology by the way it’s vascular looks at the CT scan.  It’s a lot of blood vessel in it, and how it goes in and out and washes out with the contrast is so typical that’s the diagnosis. You don’t need testology. Now this makes it of course particular disease develop treatments attacking this blood vessels. And that’s the reason we see that Sorafenib, which is an inhibitor of receptors responsible for blood vessel formation are successful. That’s the reason Bevacizumab is successful. So I think you can see that the biology and the understanding what makes the tumor grow will be for us the future success for more effective treatment.

Selma R. Schimmel:

So in summary, especially in the area of GI cancers, it’s a very fertile cancer – as you use the metaphor of the highway – that these patients, especially with more advanced disease, have every opportunity to take advantage of this emerging area of targeted therapy that are very unique to the GI cancers.

Heinz-Josef Lenz:

The key message is stay tuned. We will, in the next couple of years, see a dramatic influence of the molecular understanding which translates directly into clinical benefit using drugs which are targeting a very specific genetic alterations and we will select patients who will benefit most of it.

Selma R. Schimmel:

Thank you Dr. Lenz, really for being a forerunner in this area of research, and for sharing your time with us. Associate Director for Clinical Research, Co-leader of the Gastrointestinal Program USC/Norris Comprehensive Cancer Center, and Professor of Medicine and Preventive Medicine at the Keck School of Medicine at the University of Southern California.

Heinz-Josef Lenz:

And Selma, I couldn’t thank you much because I think this is so critical for your viewers to see what’s going on and maybe feel a little bit of excitement that there is so much to come which all changes the lives of our patients.

Selma R. Schimmel:

Thank you.

END OF VIDEO