Translator: Therese Rajasekera Reviewer: Denise RQ
Hi there.
So how many of you have been affected by cancer in some way?
It's probably nearly all of you.
Either you've been affected by it or perhaps a friend or relative has.
And how many have you have heard of the amazing advances
we made in cancer therapy over the past 10 years?
Breakthroughs.
It seems like we're closer and closer to the cure every year.
But what I bet you don't know
is that over 50% of cancer clinical trials ultimately fail.
So why do they fail?
They fail because the drug's been shown
to be either not effective or perhaps to have a side effect
that is just too severe to be used in people.
So what does this mean in terms of the cost of failure?
It's tremendous.
If you think back to the 1950s, approximately 40 drugs were approved
per billion dollars spent in research and development.
Now, less than one drug is approved
per billion dollars spent in research and development.
That's a huge loss.
That's simply not sustainable in the world of industry or research.
So something really has to change.
And when you ask,
why do so many of these clinical trials fail,
at least in part, it's due to the model we're using.
In general, mouse models are used to study cancer.
And in many of the models we use in mice,
they have no immune system.
Well, that doesn't make sense.
You or I have immune systems,
so how can that be reflective of human cancer?
We also try to make cancer grow really quickly in mice
by making it happen in weeks.
But cancer in people grows over months and months, perhaps years.
Sometimes, it can take a decade for tumors to grow.
So that's not reflective of the human experience either.
The other thing we do in research when we use mice
is make all the mice look the same,
we want all the groups to be equal so that we do an experiment,
we have very few variables.
But cancer in you, and me, the other person, and the other person,
is different.
It's very heterogeneous.
So, again, not really reflective of what we see in people.
And lastly, I bet you didn't know that mice don't vomit.
So how can we know whether a drug we're trying in mice
is actually going to cause vomiting in people?
So these are huge holes that we have in the current systems
that we use to study cancer.
So when I entered veterinary school, many years ago,
I was surprised to learn
that cancer is incredibly common in the dog world.
In fact, if you look across all breeds of dog,
it's the most common cause of death.
And if you look at a dog that's 10 years of age or older,
and many of us have older dogs, they have a 50/50 shot of getting a tumor.
And as I went through vet school,
I learned that cancer in dogs actually looks a lot like cancer in people.
In fact, they get many of the same things.
They get lung cancer, bladder cancer, they get colon cancer, etc.
So really very similar on the outside.
And this really intrigued me,
so I decided to pursue further training and become a veterinary medical oncologist
something you're probably not familiar with,
a veterinarian who treats cancer.
And during my training,
I wanted to really ask
whether or not the tumors on the inside of dogs,
meaning the molecular structure of the tumor in dogs
really resembled the molecular structure of tumors that we see in people.
We kind of knew they looked the same on the outside,
but were they the same on the inside?
And so, we studied a gene called KIT in dogs,
and KIT is a gene that's frequently mutated in human cancers.
And lo and behold,
we found that KIT mutations occur
with an incredibly high frequency in many dog cancers
and they look exactly the same as they do in people.
And this really led us to believe
that not only is dog cancer very similar on the outside,
but it's also very similar on the inside.
So, this has led
to a drastically new concept in the world of clinical trials,
called integrated and comparative trials.
And this is where we leverage what we can learn in dogs with cancer
and then apply it to human experience.
So, in this setting,
a drug would be tested in dogs with cancer
before it ever got into people
to decide whether or not it was going to be effective
and perhaps whether it had side effects that we didn't really know about.
So in this setting,
dogs would come into a clinic, much like you or I,
and enter clinical trials for their cancer.
We would first ask a set of questions that are important to know:
is the drug active?
Does it have a side effect that we didn't anticipate it having?
And do we get to appropriate blood levels in the bloodstream?
And if the answer is yes,
then we say,"OK, you're good to go on the human side."
And while the initial human studies are being done,
we go back to the dogs and ask critical questions.
We ask what's the right dose?
How often should we give the drug?
Is there something we can measure in the bloodstream
that can tell us which patients
are much more likely to benefit from this drug?
And we take that information
and put it back into the human experience.
And what this does
it helps us more effectively move those drugs
that are likely to succeed forward
and take those drugs out of the pipeline
that are much more likely to fail.
And who wins by this? Everybody.
Our pets get access
to really state-of-the-art, cutting edge therapy
at little to no cost, so that's great for them.
And then humans get access to really critical information
that can impact their outcome.
And then you ask, "Well, does this really work?"
And the answer is yes.
At Ohio State alone, in our cancer clinic,
we have removed 3 drugs from the pipeline by testing them in dogs first.
One was simply not active,
one had side effects that weren't acceptable,
and one didn't even hit the target it was supposed to hit.
And all of these drugs were moved forward
based on positive results in mouse models.
But we have lots of good experiences, as well,
that have really moved us forward.
For example, in this clinical trial, we were able to show
that a new immunotherapy approach was safe in dogs
and that it made tumors shrink.
This served as the basis
for future human clinical trials for this approach.
One of the questions we often ask is,
is the drug getting to the target it needs to get to?
Because if it's not,
then there's really a very low likelihood that it's going to work.
So in this clinical trial, we were able to show
the drug made it to tumor blood vessels but not to normal blood vessels
and that it was safe to give.
We were also able to identify the dose to use,
so this information fed back to the human clinical trials
and made them more successful.
Another conundrum that's often faced during drug development
is that sometimes we come up
with analogs of the same drug that all look pretty good.
We use mouse models to predict which one should move forward.
What we found is that the mouse models
don't often predict which ones should go.
In this clinical trial, we had to pick between 3 drugs
and we put them in dogs and were able to show
that one was much more superior to the other,
And that one went forward in the human clinical trials.
Interestingly, the mouse model predicted the wrong drug.
And then lastly,
all of you I'm sure have heard of personalized cancer therapy
where a tumor comes off,
you get the genetic information that goes back to your doctor,
and then your doctor designs
a personalized cancer therapy based on that.
The roots of this actually were in dogs because recent work was able to show
that we can take dogs with cancer, biopsy their tumor,
get the genetic information back to the patients within 1 week
to be able to match the right drug to the right patient.
So in summary, I would like you to think about our best friends
in a very different way.
Dogs add so much value to our lives;
they provide service to those with disabilities,
they protect men and women in uniform,
and for many of us,
they provide true companionship and unconditional love.
But some day, a dog walking down the street
like Maggie, Sarah, Willie, and Macy,
may very well save your life for a different reason:
by participating in a clinical trial of a new drug
that ultimately impacts your cancer treatment.
Thank you.
(Applause)