Beyond the 'War,' The Future Of Cancer Treatment

The first written reference to cancer appeared in the 17th century B.C., but physicians are still struggling to understand the disease 4,000 years later. Siddhartha Mukherjee, author of The Emperor of all Maladies: A Biography of Cancer, talks about the history of cancer and the future of treatment.

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IRA FLATOW, host:

You're listening to SCIENCE FRIDAY. I'm Ira Flatow.

According to my next guest, one in three women in the U.S. and one in two men will develop cancer in their lifetime. And a quarter of all American deaths will be due to cancer.

Why after billions of dollars of research, a declaration of war on cancer that shows no overall victory in sight, should we now reset our sights on fighting this war? Do we need a new way to think about cancer?

Despite the statistics, my next guest is optimistic. He's an oncologist at Columbia University Medical Center. He has written a book on the history of cancer to help him and his patients better understand the disease.

Dr. Siddhartha Mukherjee is an assistant professor of medicine at Columbia University, and his new book is "The Emperor of All Maladies: A Biography of Cancer." Welcome to SCIENCE FRIDAY, Dr. Mukherjee.

Dr. SIDDHARTHA MUKHERJEE (Author, "The Emperor of All Maladies"): Thank you for having me.

FLATOW: Why a biography of cancer?

Dr. MUKHERJEE: Well, I started off thinking that I would write this book as a history of cancer, but there were several things that, as I wrote the book, it became something more than a history. One aspect of it is that, of course, part of the book is a memoir. This book contains some of my own understanding of cancer as I trained in cancer medicine, and historians don't generally enter their own history. So it felt as if I wasn't just writing a straight history. That would be too inert.

And secondly, it felt also as if I was looking at the same disease. For instance, breast cancer in 1950, then again in 1980 and then again in 1990. It was like drawing a portrait over time. And that is, of course, in some sense a biography, and therefore, I titled this a biography of cancer.

FLATOW: And it has - there's so many personal stories in here it's as if Oliver Sacks were writing this book. I say that as a compliment.

Dr. MUKHERJEE: I admire Oliver Sacks. You know, that's a very flattering thing to say.

FLATOW: And you chose that as your narrative?

Dr. MUKHERJEE: I did. I mean, you know, as I said, you know, I couldn't have written the story without really entering the story myself. I'm an oncologist. I see, I think, as much of the frontlines of this complex series of diseases, complex family of diseases as anyone else. And so it felt as if that I had to, you know, those stories are part of the larger picture of the story.

But, of course, as you find out, as you know, you enter the actual history of the disease the very first time. When was the word cancer first used? And also what happens next? Why are we here today? What happened to the war on cancer?

FLATOW: Yeah. What were the mistakes of the past, and are there new directions that you see we should be going in not to repeat those mistakes?

Dr. MUKHERJEE: Well, I think there are two questions. First, what were the mistakes of the past? I mean, I think the one - I mean, I'm not sure we'd call it a mistake, and I'll tell you why. But one very important thing about the past is that I think we imagined as a community of scientists, as patients, as researchers or doctors, we imagined cancer as a relative - in a much more simple way. We really didn't understand the incredible diversity that lies in the family of diseases. In other words, one breast cancer doesn't even resemble a second breast cancer, let alone one breast cancer resembling, for instance, a stomach cancer.

And this idea that there was a monolithic disease called cancer inspired the notion that you could have only one monolithic solution, you know, a lot of surgery or a huge dose, you know, of common chemotherapies. And therefore, it was a problem of the imagination in terms of their diversity of the disease.

And that, in turn, led to a political idea which was, you know, you could conquer cancer if you just poured enough resources into it. And this was back in the 1970s, and scientists, many scientists said, wait a second, we - this is like launching a rocket to the moon without understanding Newton's laws.

The second question is, well, what happens next? I think most researchers, most scientists, most physicians would agree that we are beginning to understand the so-called Newton's laws of cancer. And therefore, we're living in a very different kind of era where we understand the complexity, and therefore, the future is about dealing with that complexity and finding both therapeutic and preventive measures that deal with that complexity.

FLATOW: In what different ways can we attack it that we haven't attacked it before that might work?

Dr. MUKHERJEE: Well, some of them have already worked. It turns out that - so just to get back to a more fundamental question. What is cancer? Why do we use the word breast cancer and prostate cancer even though acknowledging those are very different diseases.

Well, one thing that's common between all forms of cancer is that it's uncontrollable growth of cells. They have several other features. I'm just talking about one very principally common feature. And it turns out that, in fact, you can - growth not that's - growth is regulated in our cells in a bunch of different ways. It's like imagining a car which has many independent accelerators and many independent breaks. And growth is regulated then by one accelerator going on in one cell, another break coming on another cell and so forth.

We now know that if you - that some cancer cells become exquisitely dependent on their growth on certain genetic pathways. And if you can target those specific pathways instead of killing growth in general, then you can actually get remarkably effective cancer therapy.

And there's a wonderful example of this in a new drug, a relatively new drug, called Gleevec, which really goes and targets the Achilles' heel of only one particular - of a series of cancers, such as a kind of leukemia. So that's one aspect of it.

And now, even until last week we're learning that there are actually other pathways that you can attack cancer by. So, for instance, you can activate the immune system in certain cancers, such as melanoma, and attack melanoma by activating your own immune system against melanoma using a drug.

So there are new mechanisms that are coming out which don't use the old paradigm, you know, let's kill all dividing cells and thereby obliterate cancer, or let's try to eliminate it as much as we can with surgery, and if that doesn't work let's do more surgery. So I think the front is constantly evolving.

FLATOW: I guess one immediate goal then would be to turn cancer, if not to cure it but to turn it into a livable chronic illness.

Dr. MUKHERJEE: Yes. In fact - and to some - in some cancers, that is -that has been achieved already. I gave you the example of this drug called Gleevec. Again, it doesn't cure this form of leukemia completely, chronic myelogenous leukemia, but in fact turns it into a chronic disease. The disease used to be called chronic myelogenous leukemia. In fact, it was chronic only - in the world of cancer, that used to be a lethal, fatal disease. But now it is truly chronic myelogenous leukemia in the sense that it is a disease that patients live with.

And we actually think that many of these patients may have no different may be no different in their lifespans than patients without the disease. So therefore it has completely converted into a chronic disease.

FLATOW: Mm-hmm. Do we need new ideas? Do we need new ways?

Dr. MUKHERJEE: Absolutely, we need new ideas and new ways. I mean, this is a problem of enormous complexity. Again, as I said, part of the problem was there was a hubristic idea in the 1970s that, oh, you know, if we just poured enough money into it, that we'd solve much of the basic mechanisms. In other words, we'd solve the Newton's(ph) laws and thereby the next step only was to design effective therapies.

We now know that that was not true. And I think that absolutely there are new ways that are coming. We've just begun to understand the genes of the cancer cell. But then beyond the cancer cell, there's the host, the human being in which the cancer is growing. So there's a lot of building of levels of complexity.

That's a - you know, I think complexities are challenges, but one shouldn't go nihilistic about the complexity. We now have several examples in which even though the tumors are very complex, in genetic ways, in ways they've lived, the ways they've survived, you can actually develop drugs against them and the tumors actually respond to those drugs.

FLATOW: 1-800-989-8255 is our number. Let's go to the phones. Let's go to Matthias(ph) in - is it Minnesota?

MATTEO(ph) (Caller): Yeah, Matteo, yes.

FLATOW: Hey. Yeah.

MATTEO: A quick question or comment (unintelligible) isn't it - it is(ph) well documented that the best way to fight cancer is just by prevention. Why don't a smart man like your guest work on prevention and try to put (unintelligible) that? As we all know, that once cancers start, it's hard to stop those. So prevention is the key.

FLATOW: All right, let me get a response. Thank you, Matteo.

Dr. MUKHERJEE: Well, absolutely. There's no doubt that prevention is the key. But what I would - and in fact, it is - that all of us are also working on prevention. It used to be in the old days that prevention and treatment used to live in separate silos. There used to be a silo called prevention, one box called prevention and one box called treatment, and never the twain did meet. In fact, that world(ph) is old. It is not true anymore.

I'll give you a couple of good examples. The drug tamoxifen was originally invented as a treatment for estrogen receptor-positive breast cancer. In fact, very powerful trials, massive, enormous trials have shown that in the appropriately selected population of women, tamoxifen can work as a prevention against breast cancer.

The whole notion that we've solved the genomes of many of these patients who would have a predisposition to getting cancer, to find oncogenes -again, you might imagine that that discovery is really directed towards treatment, but it's not. That same mechanism of finding what the oncogenes are might be able - is being used, actually, for instance, in colon cancer to diagnose very early forms of colon cancer. So in fact, the interrelatedness of prevention and treatment research is enormous.

And the National Cancer Institute has recognized this. And in fact, there are very few people, I think, cancer biologists, who don't -haven't got at least one hat on which thinks about prevention while having another hat on which thinks about treatment. And this is there's a lot of back and forth, much more so than you might imagine, much more so certainly has been the case in the past.

FLATOW: Eric in Sioux Falls, South Dakota. Hi.

ERIC (Caller): Hi. A quick question for you, and I'll take it off air. I am just curious in if we were to look back in prehistoric times and evolution and how changes occurred in different species, would that not be similar to what is occurring with cancer? Is it not changing the physiological or physical...

FLATOW: So you're saying it's that really a disease, it's just a mutation that's occurring.

ERIC: Correct.

Dr. MUKHERJEE: Well, I'm trying to understand the question. But in my book, in "The Emperor of All Maladies" I actually talk about the evolution of cancer within the organisms. In other words, cancers evolve even within a single patient. You have, you know, it's like evolution captured in a little box, as it were. So if your question is, is cancer caused by mutations, absolutely, it's caused by mutations. And those mutations actually mimic the same kind of processes that happen in a much more macrocosmic, on a grand scale, when organisms evolve. There's a mimicry going on in that there's a parallel between those two processes.

But it's in the case of cancer, of course, those mutations are have a pathological quality. They invade - cancer cells invade. They take up residence in other organs. They metastasize and ultimately lead to morbidity and mortality.

FLATOW: You mentioned in on your article and parts of your book the theory that cancer may have stem cells. There's an idea that there may be stem cells. And if you just leave one little cancer stem cell around, it could just then multiply back and show up again. And that's why people may go out of remission, because you haven't gotten all those tiny little stem cells.

Dr. MUKHERJEE: Absolutely.

FLATOW: Is that still an accepted idea or is that...

Dr. MUKHERJEE: Yes, it's you know, it's turning out, once again again, we're facing a question about what is general and what is not general. I'll give you a good example. Now, in certain cancers, particularly in leukemias, it turns out that there are very clearly identifiable populations of these stem cells, which are like roots. And if you cut off the tree or if the winter comes and it takes care of the, you know, the entire tree dies off, when spring comes again, the roots cause the tree to sprout up again.

Now, in leukemia, there's one such population of cells. In other cancers, to give you another example, melanoma, there appear to be either every cell has this potential or it seems to be that this discrimination between the root and the shoot of the tumor is relatively arbitrary. So it really - again, once again, it's coming down to a question of - it really varies from cancer to cancer. But certainly some cancers have stem cells, and eradicating those cells, we think, will be the key to fully curing the disease.

FLATOW: Talking with Siddhartha Mukherjee, who is author of the new book "The Emperor of All Maladies: A Biography of Cancer," on SCIENCE FRIDAY from NPR. I'm Ira Flatow.

In the few minutes left that we have to discuss, I get the impression from you, even though you've written this huge history of cancer, you certainly don't feel that the final chapters have been written about this, and you appear to be optimistic despite all these years.

Dr. MUKHERJEE: Absolutely. I mean, you know, the idea of calling this book "The Emperor All Maladies" was to signify that we are sort of in, really in mid-pitch of our long and complex struggle against cancer. And as I just pointed out to you, I mean literally last week, Ira, there were new drugs approved by the FDA, which open up completely new doors.

FLATOW: Let's talk about it. It's about - for fighting melanoma, right?

Dr. MUKHERJEE: Yes.

FLATOW: And what do these drugs do that others did not?

Dr. MUKHERJEE: Well, for a long time we knew that melanoma and certain other tumors were controlled or could be controlled by our immune system, because there were cases, very rare but very provocative cases of patients in which their own tumors suddenly disappeared without any chemotherapy. So - and this idea that the immune system was playing a role had been around for a long time. It's true for several other cancers, but not all cancers, as far as we know.

And then - but there were many early attempts to try to activate the immune system against cancer, and they had not worked out. And the field was sort of full of dead and - you know, there was the death and debris of scientists. But then, through a series of long investigations, it turns out there are certain drugs that can activate the immune system, and in this case work against melanoma.

Now, it's important to know that these are drugs early in development. They extend life by four months, five months, six months in very advanced metastatic melanoma. Now, if you take that same drug and you apply it to a more early stage melanoma, you know, will you get that extension of life? Will you get more? Will you get even, you know, synergistic effects with other drugs? It really is opening up a universe. And this is happening in many different forms in different kinds of drugs.

FLATOW: So using drugs to help tweak up the immune system so you'll fight it yourself.

Dr. MUKHERJEE: That's right.

FLATOW: Because from what I'm reading in your book, there may be cancer cells all the time in our bodies that we're continually fighting. They don't pop up until they get big enough.

Dr. MUKHERJEE: Exactly. I mean, one of the questions in the book that I raise and, you know, this is from the work of other scientists, really the question is why we aren't all the time exploding with cancer. And the answer is there are several mechanisms that prevent ourselves from so-called exploding with cancer. The body is, you know, there are genes that act as barriers against the growth of cancer cells. But beyond just the genes themselves, there are immunological mechanisms that act as barriers.

So each of these points - I don't want to overemphasize the immunological mechanism. I think that that's just one part of many, many new different strategies that can be used to attack cancer in the 21st century, and they will be different from the ways that we attacked cancer or various forms of cancer in the 20th century. And that's what makes me optimistic.

FLATOW: Well, that's a good way to end this segment. Thank you very much for taking time to be with us today.

Dr. MUKHERJEE: It's a real pleasure. Thank you so much.

FLATOW: Good luck - Dr. Siddhartha Mukherjee, his new book is "The Emperor of All Maladies: A Biography of Cancer."

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