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上次更新日期:2014-12-30

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「Adam de la Zerda:打贏癌症這場戰役」- We Can Start Winning the War against Cancer


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"We're declaring war against cancer, and we will win this war by 2015."

This is what the US Congress and the National Cancer Institute declared just a few years ago, in 2003. Now, I don't know about you, but I for one, I don't buy that. I don't think we quite won this war yet, and I don't think anyone here will question that. Now, I will argue that a primary reason why we're not winning this war against cancer is because we're fighting blindly.

I'm going to start by just showing you a little story about a good friend of mine. His name is Ehud, and a few years ago, Ehud was diagnosed with brain cancer. And not just any type of brain cancer: he was diagnosed with one of the most deadly forms of brain cancer. In fact, it was so deadly that the doctors told him that they only have 12 months, and during those 12 months, they have to find a treatment. They have to find a cure, and if they cannot find a cure, he will die.

Now, the good news, they said, is that there are tons of different treatments to choose from, but the bad news is that in order for them to tell if a treatment is even working or not, well, that takes them about three months or so. So they cannot try that many things.

Well, Ehud is now going into his first treatment, and during that first treatment, just a few days into that treatment, I'm meeting with him, and he tells me, "Adam, you know, I think this is working. I think we really lucked out here. Something is happening."

And I ask him, "Really? How do you know that, Ehud?"

And he says, "Well, I feel so terrible inside. Something's gotta be working up there. It just has to."

Well, unfortunately, three months later, we got the news, it didn't work. And so Ehud goes into his second treatment. And again, the same story. "It feels so bad, something's gotta be working there." And then three months later, again we get bad news. Ehud is going into his third treatment, and then his fourth treatment. And then, as predicted, Ehud dies.

Now, when someone really close to you is going through such a huge struggle, you get really swamped with emotions. A lot of things are going through your head. For me, it was mostly outrage. I was just outraged that, how come this is the best that we can offer? And I started looking more and more into this. As it turns out, this is not just the best that doctors could offer Ehud. It's not just the best doctors could offer patients with brain cancer generally. We're actually not doing that well all across the board with cancer.

I picked up one of those statistics, and I'm sure some of you have seen those statistics before. This is going to show you here how many patients actually died of cancer, in this case females in the United States, ever since the 1930s. You'll notice that there aren't that many things that have changed. It's still a huge issue. You'll see a few changes, though. You'll see lung cancer, for example, on the rise. Thank you, cigarettes. And you'll also see that, for example, stomach cancer once used to be one of the biggest killers of all cancers, is essentially eliminated. Now, why is that? Anyone knows, by the way? Why is it that humanity is no longer struck by stomach cancer? What was the huge, huge medical technology breakthrough that came to our world that saved humanity from stomach cancer? Was it maybe a new drug, or a better diagnostic? You guys are right, yeah. It's the invention of the refrigerator, and the fact that we're no longer eating spoiled meats. So the best thing that happened to us so far in the medical arena of cancer research is the fact that the refrigerator was invented.

And so—yeah, I know. We're not doing so well here. I don't want to miniaturize the progress and everything that's been done in cancer research. Look, there is like 50-plus years of good cancer research that discovered major, major things that taught us about cancer. But all that said, we have a lot of heavy lifting to still do ahead of us.

Again, I will argue that the primary reason why this is the case, why we have not done that remarkably well, is really we're fighting blindly here. And this is where medical imaging comes in. This is where my own work comes in.

And so to give you a sense of the best medical imaging that's offered today to brain cancer patients, or actually generally to all cancer patients, take a look at this PET scan right here. Let's see. There we go.

So this is a PET/CT scan, and what you'll see in this PET/CT scan is the CT scan will show you where the bones are, and the PET scan will show you where tumors are. Now, what you gonna see here is essentially a sugar molecule that was added a small little tag that is signaling to us outside of the body, "Hey, I'm here." And those sugar molecules are injected into these patients by the billions, and they're going all over the body looking for cells that are hungry for sugar. You'll see that the heart, for example, lights up there. That's because the heart needs a lot of sugar. You'll also see that the bladder lights up there. That's because the bladder is the thing that's clearing the sugar away from our body. And then you'll see a few other hot spots, and these are in fact the tumors.

Now, this is a really a wonderful technology. For the first time, it allowed us to look into someone's body without picking up each and every one of the cells and putting them under the microscope, but in a noninvasive way allowing us to look into someone's body and ask, "Hey, has the cancer metastasized? Where is it?" And the PET scans here are showing you very clearly where are these hot spots, where is the tumor.

So as miraculous as this might seem, unfortunately, well, it's not that great. You see, those small little hot spots there. Can anyone guess how many cancer cells are in any one of these tumors? So it's about 100 million cancer cells, and let me make sure that this number sunk in. In each and every one of these small little blips that you're seeing on the image, there needs to be at least 100 million cancer cells in order for it to be detected. Now, if that seemed to you like a very large number, it is a very large number. This is in fact an incredibly large number, because what we really need in order to pick up something early enough to do something about it, to do something meaningful about it, well, we need to pick up tumors that are a thousand cells in size, and ideally just a handful of cells in size. So we're clearly pretty far away from this.

So we're going to play a little experiment here. I'm going to ask each of you to now play and imagine that you are brain surgeons. And you guys are now at an operating room, and there's a patient in front of you, and your task is to make sure that the tumor is out. So you're looking down at the patient and as you're looking down at the patient, the skin and the skull have already been removed, so you're looking at the brain. And all you know about this patient is that there's a tumor about the size of a golf ball or so in the right frontal lobe of this person's brain. And that's more or less it. So you're looking down, and unfortunately everything looks the same, because brain cancer tissue and healthy brain tissue really just look the same. And so you're going in with your thumb, and you start to press a little bit on the brain, because tumors tend to be a little harder, stiffer, and so you go in and go a little bit like this and say, "It seems like the tumor is right there." Then you take out your knife and start cutting the tumor piece by piece by piece. And as you're taking the tumor out, then you're getting to a stage where you think, "Alright, I'm done. I took out everything." And at this stage, if that's—so far everything sounded, like, pretty crazy—you're now about to face the most challenging decision of your life here. Because now you need to decide, should I stop here, let this patient go, risking that there might be some leftover cancer cells behind that I just couldn't see, or should I take away some extra margins, typically about an inch or so around the tumor just to be sure that I removed everything?

So this is not a simple decision to make, and unfortunately this is the decision that brain cancer surgeons have to take every single day as they're seeing their patients.

And so I remember talking to a few friends of mine in the lab, and we say, "Boy, there's got to be a better way." But not just like you tell a friend that there's got to be a better way. No, no, no. There's just got to be a better way here. This is just incredible.

And so we looked back. Remember those PET scans I told you about, the sugar and so on. We said, hey, how about instead of using sugar molecules, let's maybe take tiny, tiny little particles made of gold, and let's program them with some interesting chemistry around them. Let's program them to look for cancer cells. And then we will inject these gold particles into these patients by the billions again, and we'll have them go all over the body, and just like secret agents, if you will, go and walk by every single cell in our body and knock on the door of that cell, and ask, "Are you a cancer cell or are you a healthy cell? If you're a healthy cell, we're moving on. If you're a cancer cell, we're sticking in and shining out and telling us, "Hey, look at me, I'm here." And they'll do it through some interesting cameras that we developed in the lab. And once we see that, then maybe we can guide brain cancer surgeons towards taking only the tumor and leaving the healthy brain alone. And so we've tested that, and boy, this works well.

So I'm going to show you an example now. What you're looking at here is an image of a mouse's brain, and we've implanted into this mouse's brain a small little tumor. And so this tumor is now growing in this mouse's brain, and then we've taken a doctor and asked the doctor to please operate on the mouse as if that was a patient, and take out piece by piece out of the tumor. And while he's doing that, we're going to take images to see where the gold particles are. And so we're going to first start by injecting these gold particles into this mouse, and we're going to see right here at the very left there that image at the bottom is the image that shows where the gold particles are. You see that the nice thing is that these gold particles actually made it all the way to the tumor, and then they shine out and tell us, "Hey, we're here. Here's the tumor."

So now we can see the tumor, but we're not showing this to the doctor yet. We're asking the doctor, now please start cutting away the tumor, and you'll see here the doctor just took the first quadrant of the tumor and you see that first quadrant is now missing. The doctor then took the second quadrant, the third, and now it appears to be everything. And so at this stage, the doctor came back to us and said, "Alright, I'm done. What do you want me to do? Should I keep things as they are or do you want me to take some extra margins around?" And then we said, "Well, hang on." We told the doctor, "You've missed those two spots, so rather than taking huge margins around, only take out those tiny little areas. Take them out, and then let's take a look."

And so the doctor took them away, and lo and behold, the cancer is now completely gone. Now, the important thing is that it's not just that the cancer is completely gone from this person's brain, or from this mouse's brain. The most important thing is that we did not have to take huge amounts of healthy brain in the process. And so now we can actually imagine a world where doctors and surgeons, as they take away a tumor, they actually know what to take out, and they no longer have to guess with their thumb.

Now, here's why it's extremely important to take those tiny little leftover tumors. Those leftover tumors, even if it's just a handful of cells, they will grow to recur the tumor, for the tumor to come back. In fact, the reason why 80 to 90 percent of those brain cancer surgeries ultimately fail is because of those small little extra margins that were left positive, those small little leftover tumors that were left there.

So this is clearly very nice, but what I really want to share with you is where I think we're heading from here. And so in my lab at Stanford, my students and I are asking, what should we be working on now? And I think where medical imaging is heading to is the ability to look into the human body and actually see each and every one of these cells separately. The ability like this would allow us to actually pick up tumors way, way earlier in the process, way before it's 100 million cells inside, so we can actually do something about it.

An ability to see each and every one of the cells might also allow us to ask insightful questions. So in the lab, we are now getting to a point where we can actually start asking these cancer cells real questions, like, for example, are you responding to the treatment we are giving you or not? So if you're not responding, we'll know to stop the treatment right away, days into the treatment, not three months. And so also for patients like Ehud that are going through these nasty, nasty chemotherapy drugs, for them not to suffer through those horrendous side effects of the drugs when the drugs are in fact not even helping them. So to be frank here, we're pretty far away from winning the war against cancer, just to be realistic. But at least I am hopeful that we should be able to fight this war with better medical imaging techniques in the way that is not blind. Thank you.

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