Leukemia: Breakthrough Research Projects

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Leukemia: Breakthrough Research Projects




Guest:  Dr. Rob Stuart – Hematology/Oncology

Guest:  Dr. Dan Fernandes – Biochemistry & Molecular Biology

Host:  Dr. Linda Austin – Psychiatry


Dr. Linda Austin:  Do you ever wonder how scientists come up with great ideas?  Sometimes it happens in the most casual of settings, like when two good friends get together over a meal and start brainstorming ideas.  Every once in a while those ideas strike gold.  And in the case of cancer research, that means that lives are saved.  MUSC researchers Dr. Rob Stewart and Dr. Dan Fernandes have worked together for many years.  Dr. Stuart is a hematologist/oncologist and Dr. Fernandes is a basic science researcher in cancers of the blood.  They work together at MUSC’s Hollings Cancer Center which, recently, was designated a National Cancer Center by the National Cancer Institute.  Dr. Stuart tells the story of how one day a simple conversation over lunch led to one of their most exciting joint discoveries.


Dr. Rob Stuart:  Let me tell the story the way I remember it.  I remember buying Dan lunch.  If you buy Dan lunch, you’ve got his attention for about an hour.  I had just come back from Saudi Arabia and wanted to find out what Dan was doing, because I had missed him for about three and a half years.  So, he told me about a body of research that he was working on that was aimed at a fairly sophisticated idea that a particular protein that allows a cell to resist to death, in other words, cancer, or cells that don’t die when they’re supposed to.  He had found that this protein was over expressed, and he had a really unique mechanism that nobody else knew about, that I knew of anyway, about how that protein came to be so abundant. 


It reminded me of a disease in people, called chronic lymphocytic leukemia, where the cells don’t multiply very fast, but they don’t die when they’re supposed to.  And I said to Dan, maybe we should see if this mechanism is applicable in chronic lymphocytic leukemia.  I said I could get cells from patients, because it’s a chronic leukemia, they live a long time.  But, it’s an incurable condition.  So, I gave Dan the cells.  He worked on it in the laboratory and, sure enough, that, right now, is, I think, the absolute leading hypothesis for how these cells resist death.  That’s a very important discovery for a fairly common leukemia.  It’s the most common leukemia in the western world.  I like to tell the story because it makes me look good but Dan actually did all the work.


Dr. Linda Austin:  This is not the only time their synergy has led to great discovery.  Dr. Fernandes tells the story of another time they found a drug that showed promise for acute myeloid leukemia.


Dr. Dan Fernandes:  The other drug actually was a compound sitting on the shelf for many years.  It belonged to a class of agents that inhibit this protein called DNA topoisomerase II.  These drugs, thought to be similar drugs, were already in the clinic, and they were effective but very toxic.  So, this drug was abandoned because it was thought to be another one like the ones we already had.  Well, we took this compound and we weren’t convinced by the old data.  We went back and reinvestigated this and picked it apart enzymatically, every step of the reaction, and found that it wasn’t a copy of what was already around. 

Although it inhibited this enzyme, it did so by a very different mechanism.  And, therefore, it did not have the toxic effects of DNA damage of these previous topoisomerase II drugs.  That was their main side effect, DNA damage and secondary cancers.  This drug, although it hits that target, does not damage the DNA, and we’ve shown that.  And now, based on this evidence, we helped to partner with a pharmaceutical company, because these trials are very expensive.  They cost, sometimes, hundreds of millions of dollars, and an academic institution cannot carry these out.


So, we partnered with a pharmaceutical company.  They essentially pay for the trial, but have the marketing rights to the compound.  Now the compound is in Phase III clinical trials.  It’s essentially past the first two phases of safety and efficacy in the disease it’s aimed for, acute myeloid leukemia.  So, now it’s in Phase III, which is widespread multi-institutional trials, just to see if it’s reproducible throughout many different institutions.  We’re very positive about this, and I think this is going to turn out to be an effective compound.  And I think we pulled one from the graveyard, in a sense.  It’s going to be a very effective drug, I think, based on the Phase II data, which was very strong and very encouraging.  I think the Phase III data will be promising and we’re already starting on the application for marketing approval.


Dr. Linda Austin:  Dr. Stuart and Dr. Fernandes have devoted their professional lives to understanding and treating patients with cancers of the blood.


Dr. Rob Stuart:  Dan and I work in hematologic malignancies, blood cancers, if you will, leukemias, lymphomas, multiple myeloma.  In those areas, the approaches that we’re taking are building on previous successes.  Dan mentioned acute myeloid leukemia.  This has always been an interest of mine.  When I started research about 30 years ago, survivors were rare enough to be anecdotes, you know, did you know that this patient has been alive and in remission for three years, or four years? 


Now, younger patients have about a 40 percent probability of cure.  That’s pretty substantial progress.  However, we’ve not made as much progress in older patients with acute myeloid leukemia, in the division of about age 60 or so, despite the fact that the over 60 age group is most of the patients.  So this has now become a particular focus at the Hollings Cancer Center and MUSC. 


So, we have a very robust program of clinical trials in acute myeloid leukemia.  And, of course, I have to admit that I have a personal reason for my focus and that is that my wife developed acute myeloid leukemia in the year 2000.  And after an initial stem cell transplant, she relapsed and had to have a second stem cell transplant which, at the time, was considered, really, too toxic to undergo.  But there was a new technique, a mini stem cell transplant, or a transplant lite, and she was the first person in South Carolina to have such a transplant because she participated in a clinical trial.  And over eight years later, she is free of leukemia.


For more information about treatment and clinical trials at Hollings Cancer Center, please go to www.hcc.musc.edu.

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