Laurie Glimcher

Moonshot to Cure Cancer

Air Date: January 16, 2016

Weill Cornell Medical Dean Laurie Glimcher talks about scientific discoveries combating cancer.

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HEFFNER: I’m Alexander Heffner, your host on The Open Mind. The emperor of all maladies, cancer, is a subject we confronted recently with National Institute of Health Foundation leader Maria Freire, specifically with regard to the untapped potential of the Human Genome Project as a first line of defense against the disease.

In announcing his decision not to run in 2016, Vice President Biden called for a moonshot to cure cancer in his remaining months in office. “I know there are Democrats and Republicans on the hill who share our passion to silence this deadly disease,” Biden reflected.

Today we evaluate the prognosis for eradicating cancer in the contemporary industrial age with one of the world’s renowned immunologists, Laurie Glimcher, Dean of Weill Cornell Medicine. So of Laurie I ask, what’s the prospect of genomic research for enhanced prevention, detection, and treatment… And what are the odds that we realize that real moonshot — A cancer vaccine to rid it from the planet forever?

GLIMCHER: Well thank you Alexander, it’s a pleasure to be on your show. When I think of cancer prevention, I think of cancer vaccines, but I think more broadly of all that we can do to prevent cancer. And part of that is coming up with a vaccine that will work like the vaccines we have for hepatitis B or flu or polio. Now, the field of cancer vaccinology is actually in a very early stage and so I think it’s an, at an exciting point and I think eventually we will figure out some of the proteins on tumor cells that can be attacked just as you would attack a virus or a bacterium. We’re not there yet. When I think of vaccines, what does vaccines mean? It means you’re trying to prevent a disease. Well there are a lot of ways to prevent cancer or to treat cancer. I like to think though of making cancer a chronic disease rather than focus just on curing cancer. Think about HIV/AIDS for example, um, as an analogy.

So, HIV/AIDS from converted from a lethal disease into a chronic disease because basic scientists’ fundamental research was done that illuminated aspects of that virus and allowed the generation of therapies like antiretroviral therapies. And so now HIV/AIDS is not a lethal disease, it is a chronic disease. But most patients still have some virus in their system, right? I think if we could get to that with cancer, turn it into a chronic disease that we could control with therapies, uh, we would have come a very, very long way. So when Vice President Biden talks about a moonshot, yes, um, we need to devote and dedicate more resources to cancer, but I think we need to do it like we did it for HIV/AIDS, which is to work from the bottom up, start with fundamental research then translate that research into new therapeutics for our patients.

You know, it’s, you can compare that to um, leaving no stone unturned. The fundamental scientists, the ones who make the basic discoveries are, are turning over those stones and the translational researchers who translate those basic discoveries into new medicines for patients are looking where the stone has already been unturned.

HEFFNER: Can there be… Honestly speaking, can there be an assault on cancer without an assault or a war on carcinogens?

GLIMCHER: Let’s talk about cancer prevention, which is really what you’re saying more broadly. Statistics would have it that maybe two thirds of cancer is treatable …well let me put it a different way. The decrease in incidents of death from cancer is largely attributable to new medicines or therapeutics. Perhaps a third is attributable to changing our environment, and that includes of course smoking which I believe accounted for probably 20 percent of deaths from, certainly from lung cancer, more than that from lung cancer, but from cancer overall. There are other behavioral things that need to be done, so obesity is a risk factor for cancer. Lack of physical activity is a risk factor for cancer. And finally, changing our propensity to screen ourselves for cancer is also a preventive medicine, so breast cancer can be prevented by mammograms, cervical cancer can be cured, essentially cured if you do regular screening tests, the pap smear tests, looking for human papilloma virus and now there’s a vaccine against human papilloma virus. Every kid should have that vaccine. Look at what happened with hepatitis C. Hepatitis C was a devastating disease but because fundamental research was done in hepatitis C, it is now curable. It is now absolutely curable with new medications. So this is transformative. And hepatitis C often led to liver cancer, so just think what we can do now by screening everybody to see if they have hepatitis C and then if they do, treating them now with the drugs that cure hepatitis C. I mean we’ve, we’ve created entirely new classes of drugs thanks to very generous support over many years from the government. And we could talk a little bit later about how that support is dwindling and the impact that’s going to have on us.

HEFFNER: Let’s talk about it now.

GLIMCHER: Okay, we’ll talk about it now. So I’ve been in this business for oh, 30 years or so, and I have never seen as restricted a budget in the federal government as I have today. And this is particularly frustrating because in the last 5 to 10 years, a revolution has taken place in science and medicine. We’ve mined the human genome, we can visualize organs and tissues with astonishing clarity, we were never able to do that. We handle big data, we do sophisticated molecular imaging, all of these advances now allow us to really move forward and get discoveries that our scientists make in their laboratories into new therapeutics for patients. And at the same time, NIH funding has become very constrained. If you look at the NIH budget, it’s about 30 billion dollars. If one were to correct that for inflation, it would be now about 47 billion dollars. The budget has actually declined in real dollars 25 percent over the last decade. And that’s just unsustainable because we are losing young scientists. We are losing senior scientists who can no longer afford to run their laboratories.

HEFFNER: So if you were to give Vice President Biden direction in terms of the public policy conducive to making that budget work, what we have now work in a way that suggests we absolutely must invest more dollars, what is the transparent output that you and your colleagues most want to demonstrate to the government and to taxpayers, look, here is what we can accomplish, look at what we’ve done already?

GLIMCHER: Indeed look at what we have done already with cures for hepatitis C and making HIV/AIDS a chronic disease, but that requires a lot of funding, so just think about it this way. If we were to double the budget of the NIH like President Clinton did, we would, we would raise it to 60 billion dollars. Now that would result in a 100 dollar contribution from each American. In other words, 30 cents a day. Think about going to Starbucks or Dunkin’ Donuts and how much you spend on one cup of coffee a day. For over a year, if you drink one cup of coffee five days a week a year, you’re gonna spend 800 dollars. So this is not a big deal. Right? To double the budget is very doable and we have bipartisan support for it. We have…

HEFFNER: Despite the bipartisan support, the forces have not allowed you and your colleagues to make this effort.

GLIMCHER: I think there’s a lack of understanding which is partly our fault as scientists and physicians in not communicating well enough with the public. But there’s a lack of understanding of how important biomedical research is. So think about, let’s take, let’s take Alzheimer’s Disease as an example. We are already spending 200 billion dollars a year taking care of Alzheimer’s patients, out of a budget, of a total health care budget of about 2.9 trillion. In the year 2040, one out of every three individuals over the age of 85 is gonna have Alzheimer’s Disease and that is going to amount to a health care cost of about 1.2 trillion dollars. What is the only way to deal with that? We have got to find a way to prevent Alzheimer’s Disease, treat Alzheimer’s Disease, or at minimum delay its onset for 5 years. Look at the aging demographics of the population. And it’s a scary, scary situation.

HEFFNER: I want to take us back to cancer for a moment, if only to evaluate that communication question that you raise. Considering the environmental risk factors, what is a plausible strategy to effect change?

GLIMCHER: The four most common cancers that account for about 80 percent of all cancer deaths are lung, breast, colorectal cancer, and prostate cancer. Now think about preventive measures for those. Well when we think about lung cancer, the biggest environmental factor is without doubt smoking. Um, that would make a huge impact and has made a huge impact on the incidence of lung cancer. We have to keep pushing that and making it clear to everybody why smoking is so dangerous. I think a lot of people still don’t understand that. Left over from the tobacco companies insisting that cancer, that lung cancer had nothing to do with tobacco.

Think about colorectal cancer. If one has a routine colonoscopy at the age of 50 and then colonoscopies thereafter as the physician recommends, you could largely prevent colon cancer, you could detect it in its very earliest stages and cure it. Take cervical cancer. If you have a pap smear every year, there’s no reason to develop cervical cancer. If you have the HPV vaccine. So you’re right, there are clearly environmental factors that can decrease the incidence and death from cancer. I would still say though that the majority of cancers cannot be prevented at this point, but they can be treated and they can be treated two major ways. I, I like to think of the progress that’s been made in cancer, the, the stunning progress that’s been made over the last 5 years falls into 2 buckets. And one bucket is what Maria Freire talked about which is precision medicine, the idea that each person’s tumor is unique and has a unique genetic fingerprint or signature. And if you can develop a drug that attacks that mutant gene, you can get in cas—some cases an astonishing response, a really astonishing response. I’ll give you an example. We had a patient at Weill Cornell who came in with bladder cancer that had been spread to many different organs and this individual was, was pretty much on death, at death’s door. It was discovered that that person had a genetic mutation for which we did have a drug but which is usually, or never seen in bladder cancer, it’s usually seen in breast cancer. But cancer can no longer be classified according to the organ in which it arises. It has to be characterized in terms of the genetic mutation that exists. And this individual was put on this drug, it’s called Herceptin, and had an astonishing response to it. So that’s precision medicine.

HEFFNER: And that’s a hyper-localized approach in effect relative to a vaccine, you’re looking at a certain set of a, of a population cohort that is small.

GLIMCHER: Well it’s a diff—diff—very different approach in the sense that tumors put on the surface these proteins that are specific only to the tumor and aren’t present on normal cells. And the idea of a cancer vaccine is to immunize an individual against those tumor proteins. Precision medicine is diving into the DNA with a knowledge that everybody’s tumor has a unique genetic profile and you want to be able to identify that specific piece of DNA that has become mutated and that is driving cancer growth.

HEFFNER: You mentioned risk factors before but when you were looking at the four most, uh, frequent cancer patients, you mentioned smoking, what about the role of um, what we’re eating? Obesity? Obesity, uh, makes you um, predisposed to which cancers?

GLIMCHER: With obesity, there is an increased risk for many cancers, and here’s where diet and nutrition certainly do come in. There’s some very interesting work on the microbiome, which is the whole other universe of DNA that lives within us in our guts, on our skin, in mucosal surfaces and there’s very clear evidence that the structure of that microbiota, but particular kinds of bacteria that are there can influence somebody’s weight and this is a really exciting study that was done by uh, a researcher at Washington University named Jeff Gordon who showed that if you take the microbiota from an obese individual and put it into a mouse, that mouse will gain weight on a high fat diet. But if you put the microbiota from a lean mouse, from a lean human, into a mouse, that mouse will be resistant to high-fat diet or so-called westernized diet, a McDonald’s diet. And that tells us that manipulating this whole other genome, the microbiome, could be very, very useful in decreasing obesity, decreasing diabetes, what we call metabolic syndrome and these are all risk factors for cancer. They’re also risk factors for Alzheimer’s Disease.

HEFFNER: When you think about those risks, you, you said despite all of those risks, we are likely to encounter as a population various forms of cancer, um, that are out of, really that are out of our control.

GLIMCHER: Well in 2012, we had diagnosed about 14 million new cases of cancer and there were about 8 million cancer deaths. By 2030, the prediction is there will be about 22 million new cases of cancer and an increasing number of deaths, about 13 million, and that’s in part because of the aging demographics of the population. The biggest risk factor for cancer is aging. And as we all grow older, and the population as a whole grows older, we’re going to see more cancer. Precision medicine is one way to attack cancer and it’s proven to be very effective but, remember that like HIV/AIDS, you’re going to need combination therapies. That’s the, the lesson that has emerged, so you can get remarkable responses to a particular drug if you have a particular mutation but tumors like the HIV virus are very, very clever and they mutate and become resistant to it. So the key to HIV/AIDS was to say let’s give a patient multiple different therapies at the same time and that makes the virus much less likely to mutate. That’s the next frontier in precision medicine. Let’s figure out how many mutations a patient has and whether we can attack them simultaneously. So precision medicine clearly is an exciting, very exciting advance and has you know, much promise in the future. The other bucket that we haven’t talked about yet, which is near and dear to my heart as an immunologist is cancer immunotherapy, which has been amazing in the last just few years. And this is a field that’s actually very old. It started with a New York City physician named William Coley, who was a surgeon and he noticed that in patients that he had operated on to remove their tumors, those patients who developed an infection afterwards tended to do better, their tumors tended to stay in remission. And so he thought well there must be something in the infection, there must be some presence in those bacteria, some, some thing that they’re making that is activating the immune system to kill the tumor. Because your immune system should kill your tumors, probably all of us have random rogue cancer cells floating around in our bodies but by and large, in the majority of cases, our immune system circulates and acts as a surveillance mechanism and kills off those few tumor cells. So Dr. Coley generated a product he called Coley’s Toxins which he administered to patients, they were bacterial lysates and some patients had a response to them. That, that soon became um, uh, passé because of the emergence of radiation therapy and chemotherapy. But it has reared its head for 30 years, immunologists have tried to say how do we activate the immune system to kill off tumors? That’s the, one of the functions of the immune system. And that has borne fruit in an amazing way just in the last few years and…

HEFFNER: In the time we have remaining, how do you scale that nationally?

GLIMCHER: As you point out, cancer vaccines are in the future. And they could be very effective. Checkpoint blockade, which is acting your immune system to recognize those cancer cells and kill them is another very promising approach and there have been some checkpoint blockade drugs out in the market now that will release the brake on T lymphocytes, the T lymphocyte is your major killer of tumor cells. And the, the advance that was made recently and the, the realization that came about was that rather than directly activating those T lymphocytes, it was better to take some pressure off the brakes by attacking receptors that inhibited T lymphocytes, and hence the generation of drugs, uh, like Yervoy and Opdivo and Ketruda and others in the pipeline that activate your T cells by releasing the brakes. And those have proven very, very powerful in diseases like melanoma, lung cancer, and many others that are still in clinical trials. So that’s, that’s another really exciting approach and then finally um, there is a recent approach of actually transferring in activated T cells that have been genetically manipulated to specifically attack the tumor. So you might say well those are rather costly and cumbersome approaches and while that’s true, I think they have made an astonishing difference to cancer patients. So I imagine that that is an area that’s going to expand further, we’re gonna get better and better at activating those T cells and making them more specific for the tumor, and I look forward to, to seeing that happen.

HEFFNER: And knowing the market forces here that really determine ultimately whether or not these treatments go into mass production, what is the obstacle to, in your mind, outside of the necessity to be funded, what is the obstacle, um, what is the barrier in your way from making these, uh, immunotherapies available to the widest population?

GLIMCHER: Checkpoint blockers are available to the majority of the population. They are expensive but you know, when you think about it, it costs a pharmaceutical company about 2.5 billion dollars to develop a drug and only perhaps 20 percent of drugs actually are revenue-generating for a company. So, when you think of the costs of cancer care, one can imagine that drugs like checkpoint blockers or transfer of these T lymphocytes are actually cost-saving, just as treatments for hepatitis C, while expensive, overall save money by preventing hepatitis and hep—hepatocarcinoma in patients. But this is a conversation I think we all need to have about uh, cost of drugs and making them affordable to not just all Americans but all citizens of the world, and that is an important goal that we should strive for.

HEFFNER: Let’s say you had all the money in the world, right? What would be your prescription… By 2020 or whatever date you want to set to banishing cancer?

GLIMCHER: I’d rather use the term make cancer a chronic disease than banish—banish cancer. The National Cancer Institute asked for a budget of 5.8 billion this year. President Obama suggested a budget of 5.1 billion. If you think of the amount of funding that was put into HIV/AIDS, that worked. It worked. It worked because it brought brilliant scientists into the field, who discovered basic things about the HIV virus that allowed them and the translational researchers and the clinicians to come up with new drugs, and the pharmaceutical companies to come up with new drugs. Right now the NIH budget is, in contrast to a country like China where they’re pouring money into basic research, the NIH budget is leading to an exit of the most talented scientists and researchers from academic medical centers and biomedical research institutes. We just can’t allow that to happen. Because once you close down your laboratory, you can’t just rev it up again if you’re able to finally get a grant. So academic medical centers have turned to other sources for funding. They’ve turned to the private sector for funding and they’ve turned to philanthropists for funding. And I think that’s great. I think that the marriage of academic medical centers and academicians with the private sector is a very, is a marriage made in heaven because it’s the best way to get basic discoveries from the laboratory into new therapeutics for our patients, so…

HEFFNER: We’ll have to leave it there, but thank you so much Laurie for educating us today on the future of cancer.

GLIMCHER: My pleasure.

HEFFNER: And thanks to you in the audience. I hope you join us again next time for a thoughtful excursion into the world of ideas. Until then, keep an open mind. Please visit The Open Mind website at Thirteen.org/openmind to view this program online or to access over 1,500 other interviews. And do check us out on Twitter and Facebook @OpenMindTV for updates on future programming.