Subtitles section Play video
-
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.