TED Talks | 李威廉：我們能藉著飲食餓死癌症嗎？
William Li heads the Angiogenesis Foundation, a nonprofit that is re-conceptualizing global disease fighting.
８種Made In Taiwan超級防癌食物 ( 更多請看 康健：不讓癌症找上你 特刊 2012-10-15 )
Good afternoon.There’s a medical revolution happening all around us,and it’s one that’s going to help us conquersome of society’s most dreaded conditions,including cancer.The revolution is called angiogenesis,and it’s based on the processthat our bodies use to grow blood vessels.
So why should we care about blood vessels?Well, the human body is literally packed with them:60,000 miles worth in a typical adult.End to end, that would form a linethat would circle the earth twice.The smallest blood vessels are called capillaries;we’ve got 19 billion of them in our bodies.And these are the vessels of life, and,as I’ll show you,they can also be the vessels of death.Now the remarkable thing about blood vesselsis that they have this abilityto adapt to whatever environment they’re growing in.For example, in the liver they form channelsto detoxify the blood;in the lung they line air sacs for gas exchange;in muscle they corkscrew so that muscles can contractwithout cutting off circulation;and in nerves they course along like power lines,keeping those nerves alive.We get most of these blood vesselswhen we’re actually still in the womb,And what that means is that as adults,blood vessels don’t normally grow.Except in a few special circumstances:In women, blood vessels grow every monthto build the lining of the uterus;during pregnancy, they form the placenta,which connects mom and baby.And after injury, blood vesselsactually have to grow under the scabin order to heal a wound.And this is actually what it looks like,hundreds of blood vesselsall growing toward the center of the wound.
So the body has the ability to regulatethe amount of blood vessels that are present at any given time.It does this through an elaborateand elegant system of checks and balances,stimulators and inhibitors of angiogenesis,such that, when we need a brief burst of blood vessels,the body can do this by releasing stimulators,proteins called angiogenic factorsthat act as natural fertilizerand stimulate new blood vessels to sprout.And when those excess vessels are no longer needed,the body prunes them back to baselineusing naturally occurring inhibitors of angiogenesis.Now there are other situations where we start beneath the baselineand we need to grow more blood vessels just to get back to normal levels –for example, after an injury –and a body can do that too,but only to that normal level,that set point.
But what we now know is that for a number of diseases,there are defects in the systemwhere the body can’t prune back extra blood vesselsor can’t grow enough new onesin the right place at the right time.And in these situations, angiogenesisis out of balance.And when angiogenesis is out of balance,a myriad of diseases result.For example, insufficient angiogenesis –not enough blood vessels –leads to wounds that don’t heal, heart attacks,legs without circulation, death from stroke,nerve damage.And on the other end, excessive angiogenesis –too many blood vessels — drives disease,and we see this in cancer, blindness,arthritis, obesity,Alzheimer’s disease.In total, there are more than 70 major diseasesaffecting more than a billion people worldwide,that all look on the surface to be different from one another,but all actually shareabnormal angiogenesisas their common denominator.And this realization is allowing usto reconceptualizethe way that we actually approach these diseasesby controlling angiogenesis.
Now I’m going to focus on cancerbecause angiogenesis is a hallmark of cancer,every type of cancer.So here we go.This is a tumor: dark, gray, ominous massgrowing inside a brain.And under the microscope, you can seehundreds of these brown staining blood vessels,capillaries that are feeding cancer cells,bringing oxygen and nutrients.But cancers don’t start out like this.And, in fact, cancers don’t start outwith a blood supply.They start out as small, microscopic nests of cellsthat can only grow toone half a cubic millimeter in size;that’s the tip of a ballpoint pen.Then they can’t get any larger because they don’t have a blood supply,so they don’t have enough oxygen or nutrients.
In fact, we’re probably forming thesemicroscopic cancers all the time in our body.Autopsy studies from people who died in car accidentshave shown that about 40 percent of womenbetween the ages of 40 and 50actually have microscopiccancers in their breasts,about 50 percent of men in their 50s and 60shave microscopic prostate cancers,and virtually 100 percent of us,by the time we reach our 70s,will have microscopic cancers growing in our thyroid.Yet, without a blood supply,most of these cancerswill never become dangerous.Dr. Judah Folkman, who was my mentorand who was the pioneer of the angiogenesis field,once called this “cancer without disease.”
So the body’s ability to balance angiogenesis,when it’s working properly,prevents blood vessels from feeding cancers.And this turns out to beone of our most important defense mechanismsagainst cancer.In fact, if you actually block angiogenesisand prevent blood vessels from ever reaching cancer cells,tumors simply can’t grow up.But once angiogenesis occurs,cancers can grow exponentially.And this is actually howa cancer goes from beingharmless to deadly.Cancer cells mutateand they gain the ability to releaselots of those angiogenic factors, natural fertilizer,that tip the balance in favor of blood vesselsinvading the cancer.And once those vessels invade the cancer,it can expand, it can invade local tissues.And the same vessels that are feeding tumorsallow cancer cells to exit into the circulationas metastases.And, unfortunately, this late stage of canceris the one at which it’s most likelyto be diagnosed,when angiogenesis is already turned onand cancer cells are growing like wild.
So, if angiogenesisis a tipping pointbetween a harmless cancer and a harmful one,then one major part of the angiogenesis revolutionis a new approach to treating cancerby cutting off the blood supply.We call this antiangiogenic therapy,and it’s completely different from chemotherapybecause it selectively aimsat the blood vessels that are feeding the cancers.And we can do this becausetumor blood vessels are unlike normal, healthy vesselswe see in other places of the body:They’re abnormal;they’re very poorly constructed;and, because of that, they’re highly vulnerableto treatments that target them.In effect, when we give cancer patientsantiangiogenic therapy –here, an experimental drug for a glioma,which is a type of brain tumor –you can see that there are dramatic changes that occurwhen the tumor is being starved.Here’s a woman with a breast cancerbeing treated with the antiangiogenic drug called Avastin,which is FDA approved.And you can see that the halo of blood flowdisappears after treatment.
Well, I’ve just shown youtwo very different types of cancerthat both responded to antiangiogenic therapy.So, a few years ago, I asked myself,”Can we take this one step furtherand treat other cancers,even in other species?”So here is a nine year-old boxer named Milowho had a very aggressive tumorcalled a malignant neurofibroma growing on his shoulder.It invaded into his lungs.His veterinarian only gave him three months to live.So we created a cocktail of antiangiogenic drugsthat could be mixed into his dog foodas well as an antiangiogenic creamthat could be applied on the surface of the tumor.And within a few weeks of treatment,we were able to slow down that cancer’s growthsuch that we were ultimately able to extend milo’s survivalto six times what the veterinarian had initially predicted,all with a very good quality of life.
And we subsequently treated more than 600 dogs.We have about a 60 percent response rateand improved survival for these petsthat were about to be euthanized.So let me show you a couple ofeven more interesting examples.This is 20-year-old dolphin living in Florida,and she had these lesions in her mouththat, over the course of three years,developed into invasive squamous cell cancers.So we created an antiangiogenic paste.We had it painted on top of the cancerthree times a week.And over the course of seven months,the cancers completely disappeared,and the biopsies came back as normal.
Here’s a cancer growing on the lipof a Wuarter horse named Guinness.It’s a very, very deadly type of cancer called an angiosarcoma.It had already spread to his lymph nodes,so we used an antiangiogenic skin cream for the lipand an oral cocktail, so we could treat from the insideas well as the outside.And over the course of six months,he experienced a complete remission.And here he is six years later,Guinness, with his very happy owner.
Now, obviously, antiangiogenic therapycould be used for a wide range of cancers.And, in fact, the first pioneering treatmentsfor people, as well as dogs,are already becoming available.There’s 12 different drugs, 11 different cancer types.But the real question is:How well do these work in practice?So here’s actually the patient survival datafrom eight different types of cancer.The bars represent survival timetaken from the erain which there was only chemotherapy,or surgery, or radiation available.But starting in 2004,when antiangiogenic therapies first became available,well you can see that there has beena 70 to 100 percentimprovement in survivalfor people with kidney cancer, multiple myeloma,colorectal cancer, and gastrointestinal stromal tumors.That’s impressive.But for other tumors and cancer types,the improvements have only been modest.
So I started asking myself,”Why haven’t we been able to do better?”And the answer, to me, is obvious;we’re treating cancer too late in the game,when it’s already establishedand, oftentimes, it’s already spread or metastasized.And as a doctor, I knowthat once a disease progresses to an advanced stage,achieving a curecan be difficult, if not impossible.So I went back to the biologyof angiogenesisand started thinking:Could the answer to cancerbe preventing angiogenesis,beating cancer at its own gameso the cancers could never become dangerous?This could help healthy peopleas well as people who’ve already beaten canceronce or twiceand want to find a way to keep it from coming back.So to look for a way to prevent angiogenesis in cancer,I went back to look at cancer’s causes.And what really intrigued mewas when I saw that dietaccounts for 30 to 35 percentof environmentally caused cancers.
Now, the obvious thing is to think aboutwhat we could remove from our diet, what to strip out, take away.But I actually took a completely opposite approachand began asking: What could we be adding to our dietthat’s naturally antiangiogenic,that could boost the body’s defense systemand beat back those blood vessels that are feeding cancers?In other words, can we eat to starve cancer? (Laughter)Well, the answer’s yes,and I’m going to show you how.Our search for thishas taken us to the market, the farm and to the spice cabinet,because what we’ve discoveredis that mother nature has laced a large numberof foods and beverages and herbswith naturally occurring inhibitorsof angiogenesis.
So here’s a test system we developed.At the center is a ring from which hundreds of blood vesselsare growing out in a starburst fashion.And we can use this systemto test dietary factorsat concentrations that are obtainable by eating.So let me show you what happens when we put inan extract from red grapes.The active ingredient’s resveratrol,it’s also found in red wine.This inhibits abnormal angiogenesisby 60 percent.Here’s what happens when we added an extract from strawberries;it potently inhibits angiogenesis.And extract from soybeans.And here is a growing list of ourantiangiogenic foods and beveragesthat we’re interested in studying.For each food type,we believe that there are different potencieswithin different strains and varietals.And we want to measure this because,well, while you’re eating a strawberryor drinking tea,why not select the one that’s most potentfor preventing cancer.
So here are four different teas that we’ve tested.They’re all common ones:Chinese jasmine, Japanese sencha,Earl Grey and a special blend that we prepared.And you can see clearlythat the teas vary in their potencyfrom less potent to more potent.But what’s very coolis when we actually combined the twoless potent teas together,the combination, the blend,is more potent than either one alone.This means there’s food synergy.
Here’s some more data from our testing.Now, in the lab, we can simulate tumor angiogenesisrepresented here in a black bar.And using this system, we can test the potency of cancer drugs.So the shorter the bar,less angiogenesis, that’s good.And here are some common drugsthat have been associated with reducing the riskof cancer in people.Statins, nonsteroidal anti-inflammatory drugsand a few others,they inhibit angiogenesis too.And here are the dietary factorsgoing head to head against these drugs.You can see, they clearly hold their ownand, in some cases, they’re more potentthan the actual drugs.Soy, parsley, garlic,grapes, berries;I could go home and cook a tasty mealusing these ingredients.So imagine if we could createthe world’s first rating systemin which we could score foodsaccording to their antiangiogenic,cancer-preventative properties.And that’s what we’re doing right now.
Now, I’ve shown you a bunch of lab data,and so the real question is:What is the evidence in peoplethat eating certain foods can reduceangiogenesis in cancer?Well, the best example I knowis a study of 79,000 menfollowed over 20 years,in which it was found that men who consumedcooked tomatoes two to three times a weekhad up to a 50 percent reductionin their risk of developing prostate cancer.Now, we know that tomatoes are a good source of lycopene,and lycopene is antiangiogenic.But what’s even more interesting from this studyis that in those men who did develop prostate cancer,those who ate more servings of tomato sauceactually had fewer blood vesselsfeeding their cancer.So this human study is a prime exampleof how antiangiogenic substancespresent in food and consumed at practical levelscan impact on cancer.And we’re now studyingthe role of a healthy dietwith Dean Ornish at UCSF and Tufts Universityon the role of this healthy diet on markers of angiogenesisthat we can find in the bloodstream.
Now, obviously, what I’ve shared with you has some far-ranging implications,even beyond cancer research.Because if we’re right, it could impact on consumer education,food services, public healthand even the insurance industry.And, in fact, some insurance companiesare already beginning to think along these lines.Check out this ad from Blue Cross Blue Shield of Minnesota.And for many people around the world,dietary cancer preventionmay be the only practical solutionbecause not everybody can afford expensive end-stage cancer treatments,but everybody could benefit froma healthy diet based on local, sustainable,antiangiogenic crops.
Now, finally,I’ve talked to you about food,and I’ve talked to you about cancer,so there’s just one more disease that I have to tell you aboutand that’s obesity.Because it turns out thatadipose tissue, fat,is highly angiogenesis dependent.And, like a tumor, fat grows when blood vessels grow.So the question is: Can we shrink fatby cutting off its blood supply?So the top curve shows the body weightof a genetically obese mousethat eats nonstopuntil it turns fat, like this furry tennis ball.And the bottom curve is the weight of a normal mouse.
If you take the obese mouse and give itan angiogenesis inhibitor, it loses weight.Stop the treatment, gains the weight back.Restart the treatment, loses the weight again.Stop the treatment, it gains the weight back.And, in fact, you can cycle the weight up and downsimply by inhibiting angiogenesis.So this approach that we’re taking for cancer preventionmay also have an applicationfor obesity.The really, truly interesting thing about thisis that we can’t take these obese miceand make them lose more weightthan what the normal mouse’s weight is supposed to be.In other words, we can’t create supermodel mice.(Laughter)And this speaks to the role of angiogenesisin regulating healthy set points.
Albert Szent-Gyorgi once said that,”Discovery consists of seeing what everyone has seen,and thinking what no one has thought.”I hope I’ve convinced youthat, for diseases like cancer, obesity and other conditions,that there may be a great powerin attacking their common denominator: angiogenesis.And that’s what I think the world needs now. Thank you.
June Cohen: I have a quick question for you. So these drugs aren’t exactly …they’re not exactly in mainstream cancer treatments right now.For anyone out here who has cancer,what would you recommend?Do you recommend pursuing these treatments now, for most cancer patients?
William Li: So there are antiangiogenic treatmentsthat are FDA approved,and if you’re a cancer patientor working for one or advocating for one,you should ask about them.And there are many clinical trials.The Angiogenesis Foundation is following almost 300 companies,and there are about 100 moredrugs in that pipeline.So consider the approved ones,look for clinical trials,but then between what the doctor can do for you,we need to start asking what can we do for ourselves.And this is one of the themes that I’m talking aboutis we can empower ourselves to do the thingsthat doctors can’t do for us,which is to use knowledge and take action.And if Mother Nature has given us some clues,we think that there might be a new futurein the value of how we eat.And what we eat is really our chemotherapy three times a day.
JC: Right. And along those lines,for people who might have risk factors for cancer,would you recommend pursuing any treatments sort of prophylacticallyor simply pursuing the right dietwith lots of tomato sauce?
WL: Well, you know, there’s abundant epidemiological evidence.And I think in the information age,it doesn’t take long to go to a credible sourcelike PubMed, the National Library of Medicine,to look for epidemiological studiesfor cancer risk reductionbased on diet and based on common medications.And that’s certainly something that anybody can look into.
JC: Okay. Well, thank you so much.
(williamw.li,m.d. 李威廉) (TED防癌食物)