good afternoon. there's a medical revolutionhappening all around us, and it's one that's goingto help us conquer some 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 bodyis 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 vesselsare called capillaries. we've got 19 billion of themin 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 thingabout blood vessels is that they have this ability to adapt to whatever environmentthey're growing in.
for example, in the liver,they form channels to detoxify the blood; in the lungs, they line air sacsfor gas exchange. in muscle, they corkscrew, so that muscles can contractwithout cutting off circulation. and in nerves, they course alonglike power lines, keeping those nerves alive. we get most of these blood vessels when 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 month, to 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 scab in order to heal a wound. and this is actually what it looks like,
hundreds of blood vessels, all growingtoward the center of the wound. so the body has the ability to regulate the amount of blood vesselsthat are present at any given time. it does this through an elaborateand elegant system of checks and balances, stimulators and inhibitorsof angiogenesis, such that, when we needa brief burst of blood vessels, the body can do thisby releasing stimulators, proteins called angiogenic factors, that act as natural fertilizer,and stimulate new blood vessels to sprout.
when those excess vesselsare no longer needed, the body prunes them back to baseline, using naturally-occurringinhibitors of angiogenesis. there are other situationswhere we start beneath the baseline, and we need to grow more blood vessels,just to get back to normal levels -- for example, after an injury -- and the 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 system, where the body can't prune backextra blood vessels, or can't grow enough new onesin the right place at the right time. and in these situations,angiogenesis is 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 woundsthat 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 morethan 70 major diseases affecting more than a billionpeople worldwide, that all look on the surface to bedifferent from one another, but all actually shareabnormal angiogenesis
as their common denominator. and this realization is allowingus to re-conceptualize the way that we actuallyapproach these diseases, by controlling angiogenesis. now, i'm going to focus on cancer, because angiogenesisis a hallmark of cancer -- every type of cancer. so here we go. this is a tumor: dark, gray, ominousmass growing inside a brain.
and under the microscope, you can see hundredsof these brown-stained 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 cells, that can only grow to one halfa cubic millimeter in size. that's the tip of a ballpoint pen.
then they can't get any largerbecause they don't have a blood supply, so they don't haveenough oxygen or nutrients. in fact, we're probably formingthese microscopic cancers all the time in our body. autopsy studies from peoplewho died in car accidents have shown that about 40 percent of womenbetween the ages of 40 and 50 actually have microscopiccancers in their breasts. about 50 percent of menin their 50s and 60s have microscopic prostate cancers,
and virtually 100 percent of us,by the time we reach our 70s, will have microscopic cancersgrowing in our thyroid. yet, without a blood supply, most of these cancerswill never become dangerous. dr. judah folkman, who was my mentor and who was the pioneerof the angiogenesis field, once called this "cancer without disease." so the body's abilityto balance angiogenesis, when it's working properly,
prevents blood vesselsfrom feeding cancers. and this turns out to be one of our most importantdefense mechanisms against cancer. in fact, if you actuallyblock angiogenesis and prevent blood vesselsfrom ever reaching cancer cells, tumors simply can't grow up. but once angiogenesis occurs, cancers can grow exponentially.
and this is actually how a cancergoes from being harmless, to being deadly. cancer cells mutate, and they gain the ability to releaselots of those angiogenic factors, natural fertilizer, that tip the balance in favorof blood vessels invading the cancer. and once those vessels invade the cancer, it can expand,it can invade local tissues, and the same vesselsthat are feeding tumors
allow cancer cells to exitinto the circulation as metastases. and unfortunately,this late stage of cancer is the one at whichit's most likely to be diagnosed, when angiogenesis is already turned on, and cancer cells are growing like wild. so, if angiogenesis is a tipping point between a harmless cancerand a harmful one, then one major partof the angiogenesis revolution is a new approach to treating cancer
by cutting off the blood supply. we call this antiangiogenic therapy, and it's completely differentfrom chemotherapy, because it selectively aims at the blood vesselsthat are feeding the cancers. we can do this because tumor blood vesselsare unlike normal, healthy vessels we see in other places of the body -- they're abnormal,they're very poorly constructed, and because of that,they're highly vulnerable
to 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 aredramatic changes that occur when the tumor is being starved. here's a woman with a breast cancer, being treated with the antiangiogenicdrug called avastin, which is fda approved.
and you can seethat the halo of blood flow disappears after treatment. well, i've just shown youtwo very different types of cancer that both respondedto 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-oldboxer named milo, who had a very aggressive tumor
called a malignant neurofibromagrowing on his shoulder. it invaded into his lungs. his veterinarian only gave himthree months to live. so we created a cocktailof antiangiogenic drugs that could be mixed into his dog food, as well as an antiangiogenic cream, that could be appliedon the surface of the tumor. and within a few weeks of treatment, we were able to slow downthat cancer's growth,
such that we were ultimatelyable to extend milo’s survival to six times what the veterinarianhad initially predicted, all with a very good quality of life. and we've subsequently treatedmore than 600 dogs. we have about a 60 percent response rate, and improved survival for these pets that were about to be euthanized. so let me show you a coupleof even more interesting examples. this is 20-year-old dolphinliving in florida,
and she had these lesions in her mouth that, over the course of three years, developed into invasivesquamous 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 lip
of a quarter horse named guinness. it's a very, very deadly typeof cancer called an angiosarcoma. it had already spread to his lymph nodes, so we used an antiangiogenicskin cream for the lip, and the oral cocktail, so we could treatfrom the inside as 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.
(applause) now obviously, antiangiogenic therapycould be used for a wide range of cancers. and in fact, the firstpioneering treatments for people as well as dogs, are already becoming available. there are 12 different drugs,11 different cancer types. but the real question is: how well do these work in practice? so here's actuallythe patient survival data
from eight different types of cancer. the bars represent survival time taken from the era in whichthere was only chemotherapy, or surgery, or radiation available. but starting in 2004, when antiangiogenic therapiesfirst became available, you can see that there has been a 70to 100 percent improvement in survival for 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 cancertoo late in the game, when it's already established, and oftentimes, it's alreadyspread or metastasized.
and as a doctor, i know that once a disease progressesto an advanced stage, achieving a cure can be difficult,if not impossible. so i went back to the biologyof angiogenesis, and started thinking: could the answer to cancerbe preventing angiogenesis, beating cancer at its own game, so the cancers could neverbecome dangerous? this could help healthy people, as well as people who've alreadybeaten cancer once or twice,
and want to find a wayto keep it from coming back. so to look for a way to preventangiogenesis in cancer, i went back to look at cancer's causes. and what really intrigued me, was when i saw that dietaccounts for 30 to 35 percent of 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 tooka completely opposite approach,
and began asking: what couldwe be adding to our diet that's naturally antiangiogenic, and that could boostthe body's defense system, and beat back those blood vesselsthat are feeding cancers? in other words, can we eatto starve cancer? (laughter) well, the answer is yes,and i'm going to show you how. and our search for thishas taken us to the market, the farm and to the spice cabinet,
because what we've discovered is that mother naturehas laced a large number of foods and beverages and herbs with naturally-occurringinhibitors of angiogenesis. 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 factors at concentrationsthat are obtainable by eating.
let me show you what happens when we put in an extract from red grapes. the active ingredient is resveratrol, it's also found in red wine. this inhibits abnormal angiogenesis, by 60 percent. here's what happens when we addedan extract from strawberries. it potently inhibits angiogenesis. and extract from soybeans.
and here is a growing list of antiangiogenic foods and beveragesthat we're interested in studying. for each food type, we believe that there aredifferent potencies within different strains and varietals. and we want to measure this because, well, while you're eating a strawberry or drinking tea, why not select the one that's most potent
for preventing cancer? so here are four different teasthat we've tested. they're all common ones:chinese jasmine, japanese sencha, earl grey and a special blendthat we prepared, and you can see clearlythat the teas vary in their potency, from less potent to more potent. but what's very cool is when we combinethe two less 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 cansimulate tumor angiogenesis, represented here in a black bar. and using this system, we can testthe potency of cancer drugs. so the shorter the bar, the less angiogenesis -- that's good. and here are some common drugs that have been associated with reducingthe risk of cancer in people.
statins, nonsteroidalanti-inflammatory drugs, and a few others --they inhibit angiogenesis, too. and here are the dietary factors going head-to-head against these drugs. you can see they clearly hold their own, and 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. imagine if we could createthe world's first rating system,
in which we could score foods according 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 people that eating certain foods can reduceangiogenesis in cancer? well, the best example i know is a study of 79,000 menfollowed over 20 years,
in which it was found that menwho consumed cooked tomatoes two to three times a week, had up to a 50 percent reduction in their risk of developingprostate cancer. now, we know that tomatoesare a good source of lycopene, and lycopene is antiangiogenic. but what's even moreinteresting from this study, is that in those men who diddevelop prostate cancer, those who ate moreservings of tomato sauce,
actually had fewer blood vesselsfeeding their cancer. so this human study is a prime example of how antiangiogenic substances presentin food and consumed at practical levels, can have an impact on cancer. and we're now studyingthe role of a healthy diet -- with dean ornish at ucsfand tufts university -- the role of this healthy dieton markers of angiogenesis that we can find in the bloodstream. obviously, what i've shared with youhas some far-ranging implications,
even beyond cancer research. because if we're right,it could impact consumer education, food services, public health and even the insurance industry. and in fact, some insurance companies are already beginningto think along these lines. check out this ad from bluecrossblueshield of minnesota. for many people around the world, dietary cancer preventionmay be the only practical solution,
because not everybody can affordexpensive end-stage cancer treatments, but everybody could benefitfrom a 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 diseasethat i have to tell you about, and that's obesity. because it turns outthat adipose tissue -- fat --
is highly angiogenesis-dependent. and like a tumor, fat growswhen blood vessels grow. so the question is: can we shrink fatby cutting off its blood supply? the top curve shows the body weightof a genetically obese mouse that eats nonstop until it turns fat, like this furry tennis ball. and the bottom curveis the weight of a normal mouse. if you take the obese mouse
and give it an angiogenesisinhibitor, it loses weight. stop the treatment, gains the weight back.restart the treatment, loses the weight. stop the treatment,it gains the weight back. and, in fact, you can cyclethe weight up and down simply by inhibiting angiogenesis. so this approach that we're takingfor cancer prevention may also have an application for obesity. the truly interesting thing about this is that we can't take these obese mice
and make them lose more weight than what the normal mouse's weightis supposed to be. in other words,we can't create supermodel mice. and this speaks to the roleof angiogenesis in regulating healthy set points. albert szent-gyã¶rgi once said, "discovery consists of seeingwhat everyone has seen, and thinking what no one has thought." i hope i've convinced you
that for diseases like cancer,obesity and other conditions, there may be a great power in attacking their commondenominator: angiogenesis. and that's what i thinkthe world needs now. thank you. june cohen: i havea quick question for you. jc: so these drugs aren't exactlyin mainstream cancer treatments right now. for anyone out here who has cancer,what would you recommend? do you recommend pursuing thesetreatments now, for most cancer patients?
william li: there areantiangiogenic treatments that are fda approved, and if you're a cancer patient, or working for one or advocating for one,you should ask about them. and there are many clinical trials. the angiogenesis foundationis following almost 300 companies, and there are about 100 moredrugs in that pipeline. so, consider the approved ones, look for clinical trials,
but then betweenwhat the doctor can do for you, we need to start askingwhat can we do for ourselves. this is one of the themesi'm talking about: we can empower ourselves to do the things that doctorscan't do for us, which is to use knowledge and take action. and if mother naturehas given us some clues, we think there might be a new futurein the value of how we eat, and what we eat is reallyour chemotherapy three times a day.
jc: right. and along those lines, for people who might haverisk factors for cancer, would you recommend pursuingany treatments prophylactically, or simply pursuing the right diet, with lots of tomato sauce? wl: well, you know, there's abundantepidemiological evidence, and i think in the information age, it doesn't take long to goto a credible source like pubmed, the national library of medicine,
to look for epidemiological studiesfor cancer risk reduction based on diet and basedon common medications. and that's certainly somethingthat anybody can look into. jc: okay. well, thank you so much.
No comments:
Post a Comment