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Salk Scientists Find Diabetes Drug Treats Lung Cancer

Diabetes Drug Treats Lung Cancer
Salk Scientists Find Diabetes Drug Treats Lung Cancer
GUESTReuben Shaw, Associate Professor, Salk Institute for Biological Studies

CAVANAUGH: This is KPBS Midday Edition. I'm Maureen Cavanaugh. San Diego's Salk institute is still celebrating the announcement of the largest financial gift in its history, the Helmsley Charitable Trust awarded Salk $42 million to establish a center of genomic medicine. That center will be used largely for research into cancer, diabetes, and Alzheimer's. Of as it turns out, researchers have already found an unexpected Crosse over between diabetes and cancer treatment. Joining me to cross the grant and the potential cancer treatment is my guest, Reuben Shaw is associate professor at Salk institute. Welcome to the program. SHAW: Thank you, Maureen. CAVANAUGH: Let's talk first about the discovery of a drug used to treat diabetes that my work for certain lung cancers too. First of all, how did you make that connection? SHAW: Great question. So we had been interested in how to go about treating one particular subtype of lung cancers that have alterations in a particular gene. 30% of lung cancers have alterations in this gene, but the gene is lost. So we can't use the traditional route of making therapeutics against that gene because the gene is miss. So we have to find a unique vulnerability that the loss of the gene confers. CAVANAUGH: Okay. So I'm still trying to make the connection between the diabetes drug. [ LAUGHTER ] SHAW: Right, how does metabolism come in there? I cut myself off. What we found that led up to the study is that the major function, the normal function of that cancer gene was to serve as a sensor in all cells of your body for energy levels in the cell, basically how much nutrients you have. So this acts normally to reprogram the cell's metabolism. So it's just like a gas gauge in your car. This cancer gene's normal function is to sense whether you have enough energy, gas in this analogy, and if you don't, unlike the gauge in your car, it actually sends a signal and puts the gas back. So in the tumor cells that lack this particular gene, they have no idea if they have enough energy or not. So when we made that basic discovery, the concept was we could take advantage of that if we could find a drug that would lower the fuel inside the cells of the tumor. Because the normal cells of your body will all still have this gene, so they just lower their metabolism. And if turns out the main source of drugs that target metabolism don't come from cancer research but from a history of diabetes research. CAVANAUGH: Sure, absolutely. So is there any metabolic process that is similar between diabetes treatment and what you're trying to do in stopping these -- this gene from misfiring in the lung tumor? SHAW: Yes! Unexpectedly. These are kind of understandings that our lab and a number of labs around the world have only discovered in the past five or ten years. So there's much more of a commonality between all cell, how they use glucose and lipids to grow and divide. So the same drug which will lower your metabolism, improve the amount of glucose in your bloodstream, the reason it's used for diabetes is the same exact reason that when given to this subtype of cancers that lack the sense or, they don't have any idea that they're run think out of gas, and just like a car, speeding down the highway at 70 miles an hour, having no idea there's a hole in the fuel tank, the cells in the same way actually seize up and die. And all the normal cells are just fine. CAVANAUGH: It would seem to me that over and above this specific, exciting research about this particular drug and type of cancer, the overarching idea that there's this metabolic connection in cancers is astounding! I mean, it's a really big breakthrough, isn't it? SHAW: It is, it is. It's a very exciting time in the cancer research field, really only in the past couple of years has there been this reawake nothing and reemergence of these discoveries that connect metabolism with cancer. This was thought about 100 years ago and went out of favor for the better part of a 7. And it's only in the past five or ten years that evidence like this has started to come back, and only in the past five years have specific genes like this one been shown that actually the main thing they do normally is regulate metabolism. So in fact, at the end of the day, the processes that control metabolism and go wrong in diabetes are also going wrong in cancer. The understanding is that drugs used to treat diabetes can be used to treat certain forms of cancer, and conversely, these diseases are just more linked than we could have known even five years ago. CAVANAUGH: Let me take it a step further. Since diabetes is a disease that can often be regulated by diet, and this drug that regulates diabetes has been shown effective on some cancer tumors, is it possible that some cancers may be treatable by changing a patient's diet? SHAW: Yes! Well, there's actually -- that's a great question. There's a large history of literature of people trying dietary intervention, and there are definitely five or ten different type was cancer where diet is very strongly linked and bad diet will actually fuel those cancers. And this same circuit of these genes are at the heart of those behaviors as well. Improving your diet will definitely help upon improving. Exercise as well activates the same energy sensor. CAVANAUGH: Metabolism. SHAW: So metabolism in the broadest sense is actually directly related to tumor cell growth in many different contexts. CAVANAUGH: This treatment, this diabetes drug of phenformin, or a relative of it, has the potential to slow the growth of some cancer tumors but not others. Are we learning that lung cancers can be really different from patient to patient? SHAW: Absolutely. I'm glad you asked that question. This finding ties into an emerging concept in the treatments of all cancers. And it's a concept called personalized medicine. And this is very common now where you're going to treat all different type was tumors not because they're a breast tumor or colon tumor, but based on the specific genes that go wrong in each person's cancer, and we will tailor the treatment to the genes that are aberrant. I heard an ad on KPBS a few days ago, the cancer center, now offering broad treatments based on genetic profiles. Today's story is just one example of that, how for this 30% of all lung cancers that have alterations in these gene, you would use this particular diabetes drug or versions of it. And by the same token, the other 70% of lung cancers, the drug won't have very much of an effect. So we can really help focus better therapeutics for the right patients. So selecting patients and leading to more effective therapies is definitely the wave of the future. CAVANAUGH: Is it only used in cancer research, personalized medicine? SHAW: No. That's a very good point. While it gained perhaps most notoriety in cancer research in the past ten year, it spans pretty much all diseases. Most diseases have some genetic component to them, and the same way of decoding the biochemical pathways and coming up with selective drugs for that particular gene aberration extends to all diseases, cystic fibrosis. Doesn't have to be cancer. CAVANAUGH: This particular research that you've done now linking this diabetes drug to slowing certain lung cancers, are most patients going to be able to take advantage of this? The reasonable future? I mean, how long will these trials continue? How close are you to being able to use this as a therapy? SHAW: Great question. In this particular case, this drug, and analogs of it have actually been used for diabetes treatment and have already been FDA approved. So this is a rare case where it won't take five more years of development and medicinal chemistry, modifying the drugs to get it into. This week with the publication of this story, I've been in contact with clinicians in Montreal and Boston who are already filing the paperwork for phase 1 clinical trials on this subset of medications. So we're extremely excited. The teams I work with, to see in real-time that they made a discovery, and it's immediately going into the clinic, that is the most exciting part of why we pursue these studies. CAVANAUGH: I'm interested to know if you are told that you have lung cancer, how does your doctor, your oncologist discover what kind of lung cancer you have in terms of what kind of tumor might be able to be treated with a therapy such as this? SHAW: Good question. This is something that's a revolution, you know, going across the country, which will vary from hospital to hospital and site to site. But everything is sweeping that way. Depending on how advanced your tumor is, if it's not that advanced, you might not even need these advanced treatments. For advanced tumor, they will send out a panel for 15 or 30 of the particular genes altered. If it's altered, then they'll tailor the therapy. This has been done in breast cancer for years. I drug her Herceptin, it has a test where they take a sample of the patient's tumor to see if it expresses this one particular cancer gene F. It does, you go on that therapy, if it doesn't, you don't. And there's something called ER-positive breast cancer. If that gene is there, they use a drug that targets that gene. If you find out from your oncologist that your breast cancer is ER-negative, then the drug that targets ER is useless. So this personalized therapy has been used in breast cancer for the longest amount of time, but now it's moving into lung cancer and all different types. CAVANAUGH: Fascinating. I want to move onto the grant that you've just received. It made big news. It's the largest gift ever received by the Salk institute; isn't that right? SHAW: That's correct. CAVANAUGH: What areas of medicine will scientists at the Helmsley center for genomic medicine, what will they be concentrating on? SHAW: That's a great question which ties into what we've been talking about. The heart of this grant, and the principle of founding this new center is around this idea that not just cancer, but actually diabetes and Alzheimer's, and many different diseases, have a common genetic element with advances in our ability to sequence all the genes in diseased tissues. We can find out which genes are altered, and that's the concept of genomic medicine, tailoring the therapies to the patients. So the main focus within the center at Salk are going to be cancer and diabetes and Alzheimer's. But there are other disease areas that tie into it as well. So I think the common thread of this particular grant is how to turn these kind of chronic diseases and some of the underlying biologists like inflammation is a commonality of not only diabetes and obesity, but cancers as well, and Alzheimer's. So many of these link, just like the link between cancer and metabolism, they've only emerged in the past couple of years. This grant is really going to fuel studying the genes involved and then studying the biological processes across fields. So people who are specialists in cancer will be working with done specialists, and people who are specialists in stem cells will be working on people who work on Alzheimer's, and the whole intermixing and collaboration is really at the heart of what Salk is about, and what this grant is about. CAVANAUGH: It's an exciting time for researchers at Salk. How is the constitute doing in its campaign to raise $300 million? I know you wanted that. SHAW: That's right. CAVANAUGH: How is that going? SHAW: It's going incredibly well, actually. With this gift, I believe they've raised $192 million of the 300. So ahead of schedule for the target goal. Everyone couldn't be more pleased and warmed by the belief of many people in this kind of research. It's truly an exciting time in biomedical research in the world, and we're just so thankful that so many donors, particularly those at the Helmsley charitable trust, have the insight to realize that this is a window in time where we can make big strides. CAVANAUGH: Now, everybody knows that research costs money. But why are you focused on this kind of an endowment for Salk? Is it because money from other sources like the government is potentially drying up for research? SHAW: Yes. Well, unfortunately in part, that is true. Government funding for basic biomedical research has been worse than flat. So it hasn't been increasing at all, keeping with inflation, it has decreased over the past decade. CAVANAUGH: That must be so frustrating when you're making all those discoveries and links that can help you people so much. SHAW: It is. And so what it forces all universities and research institutes around the whole U.S. to do is to try to partner with other philanthropic organizations be. Many people don't realize how much biomedical research in this country across all locations is fueled by federal dollars. This is something real that comes out of our taxes, but absolutely has led to principally all the known cures of most of the known diseases. You'd be surprised. CAVANAUGH: I have to end it there. I've been speaking with Ruben Shaw, associate professor at Salk institute. Thank you very, very much for speaking with us. SHAW: Thank you very much.

Some 10 years ago, Reuben Shaw, now an associate professor at the Salk Institute for Biological Studies, discovered that a gene altered by lung cancer regulated an enzyme used to treat diabetes. He hoped there was more to the story, and he continued to theorize about the relationship between metabolic diseases like diabetes and cancer.

He wondered, for instance, if drugs designed to work on diabetes could also work on cancer. Ten years after his original discovery, Shaw is finding that the answer to that question appears to be yes.

"It suggested a potential therapeutic Achilles' heel, if you will, for tumors that have this particular genetic alteration," he said. "So then searching for what types of things might lower the metabolism of certain cells, it turns out that they're not existing cancer drugs, but actually the world of diabetes research."

Shaw and his team at Salk's new Helmsley Center for Genomic Medicine have found growing evidence that a drug called phenformin, a derivative of a widely used diabetes drug called metformin, shrank lung cancer tumors in mice and increased the animals' survival.

Shaw's team is part of a group of scientists at the research facility working to decode the genetic factors in common chronic diseases such as cancer, diabetes, Alzheimer's and Parkinson's.

According to Shaw, the amount of genetic information currently available has made the process of decoding, theorizing, testing and eventually tailoring a cure to a specific disease much more fruitful.

Claire Trageser contributed to this report.