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  • Good afternoon.

  • There's a medical revolution happening all around us,

  • and it's one that's going to help us conquer

  • some of society's most dreaded conditions,

  • including cancer.

  • The revolution is called angiogenesis,

  • and it's based on the process

  • that 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 line

  • that 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 vessels

  • is that they have this ability

  • to adapt to whatever environment they're growing in.

  • For example, in the liver they form channels

  • to detoxify the blood;

  • in the lung they line air sacs for gas exchange;

  • in muscle they corkscrew so that muscles can contract

  • without cutting off circulation;

  • and in nerves they course along like 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 vessels

  • actually 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 growing toward the center of the wound.

  • So the body has the ability to regulate

  • the amount of blood vessels that are present at any given time.

  • It does this through an elaborate

  • and 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 factors

  • that act as natural fertilizer

  • and stimulate new blood vessels to sprout.

  • And when those excess vessels are no longer needed,

  • the body prunes them back to baseline

  • using naturally occurring inhibitors of angiogenesis.

  • Now there are other situations where 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 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 system

  • where the body can't prune back extra blood vessels

  • or can't grow enough new ones

  • in 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 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 diseases

  • affecting more than a billion people worldwide,

  • that all look on the surface to be different from one another,

  • but all actually share

  • abnormal angiogenesis

  • as their common denominator.

  • And this realization is allowing us

  • to reconceptualize

  • the way that we actually approach these diseases

  • by controlling angiogenesis.

  • Now I'm going to focus on cancer

  • because angiogenesis is a hallmark of cancer,

  • every type of cancer.

  • So here we go.

  • This is a tumor: dark, gray, ominous mass

  • growing inside a brain.

  • And under the microscope, you can see

  • hundreds 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 out

  • with a blood supply.

  • They start out as small, microscopic nests of cells

  • that can only grow to

  • one 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 these

  • microscopic cancers all the time in our body.

  • Autopsy studies from people who died in car accidents

  • have shown that about 40 percent of women

  • between the ages of 40 and 50

  • actually have microscopic

  • cancers in their breasts,

  • about 50 percent of men in their 50s and 60s

  • have 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 cancers

  • will never become dangerous.

  • Dr. Judah Folkman, who was my mentor

  • and 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 be

  • one of our most important defense mechanisms

  • against cancer.

  • In fact, if you actually block angiogenesis

  • and 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 how

  • a cancer goes from being

  • harmless to deadly.

  • Cancer cells mutate

  • and they gain the ability to release

  • lots of those angiogenic factors, natural fertilizer,

  • that tip the balance in favor of blood vessels

  • invading the cancer.

  • And once those vessels invade the cancer,

  • it can expand, it can invade local tissues.

  • And the same vessels that are feeding tumors

  • allow cancer cells to exit into the circulation

  • as metastases.

  • And, unfortunately, this late stage of cancer

  • is the one at which it'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 cancer and a harmful one,

  • then one major part of 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 different from chemotherapy

  • because it selectively aims

  • at the blood vessels that are feeding the cancers.

  • And we can do this because

  • tumor blood vessels are 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 patients

  • antiangiogenic therapy --

  • here, an experimental drug for a glioma,

  • which is a type of brain tumor --

  • you can see that there are dramatic changes that occur

  • when the tumor is being starved.

  • Here's a woman with a breast cancer

  • being treated with the antiangiogenic drug called Avastin,

  • which is FDA approved.

  • And you can see that the halo of blood flow

  • disappears after treatment.

  • Well, I've just shown you

  • two very different types of cancer

  • that both responded to antiangiogenic therapy.

  • So, a few years ago, I asked myself,

  • "Can we take this one step further

  • and treat other cancers,

  • even in other species?"

  • So here is a nine year-old boxer named Milo

  • who had a very aggressive tumor

  • called 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 drugs

  • that could be mixed into his dog food

  • as well as an antiangiogenic cream

  • that 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 growth

  • such that we were ultimately able to extend milo's survival

  • to 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 rate

  • and improved survival for these pets

  • that were about to be euthanized.

  • So let me show you a couple of

  • even more interesting examples.

  • This is 20-year-old dolphin living in Florida,

  • and she had these lesions in her mouth

  • that, 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 cancer

  • three 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 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 lip

  • and an oral cocktail, so we could treat from 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 therapy

  • could be used for a wide range of cancers.

  • And, in fact, the first pioneering treatments

  • for 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 data

  • from eight different types of cancer.

  • The bars represent survival time

  • taken from the era

  • in 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 been

  • a 70 to 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 cancer too late in the game,

  • when it's already established

  • and, oftentimes, it's already spread or metastasized.

  • And as a doctor, I know

  • that once a disease progresses to an advanced stage,