- Thanks everyone for coming
to our open house today,
and for interest in our research.
I will be talking about breast cancer,
and more specifically,
how we have progressed in recent years
towards a better treatment
for metastatic breast cancer.
And I'll start off with
a short introduction
into breast cancer in general.
You may have heard that in her lifetime,
one in eight women actually
comes down with breast cancer,
so quite a lot of women, maybe
each of you has a relative
or a friend whom this happened.
Out of this one in eight
that will get breast
cancer in their lifetime,
three of those will get
what we call metastatic breast cancer,
now what exactly is that.
Metastatic breast cancer means
that the cancer has moved
from its original site,
the breast, to other parts of the body.
And specifically breast cancer,
it can be the brain, the
liver, the bones, or the lung.
And you can already
imagine that if your cancer
in any of these very important organs,
that's probably not very
good for the patient.
In general, breast cancer is staged into
five different stages.
The very first, stage zero,
is also called ductal
carcinoma in situ or DCIS,
which some of you may have
heard of that in the past.
And it means you don't
actually have a tumor yet,
but some cells in the breast are excited,
they are now going crazy
and they're just growing
where shouldn't grow and way too fast.
And this can eventually develop
into other stages of breast cancer.
Now this can actually be
detected by a mammogram,
so this is very good.
So early detection, really important.
Stage one breast cancer
means there is a tumor,
but it's comparably small
and it's just in the breast.
Stage two means now it has
moved to the lymph nodes,
the axillary lymph nodes, usually first,
so it's slowly starting to
spread through the body.
In stage three, tumor is bigger
definitely in the lymph nodes,
and maybe in other areas in the breast.
And finally, in stage
four we have metastasis,
meaning now there's
cancer cells in the brain,
in the lungs, or in other viable organs.
So let's have a look at the survival rate,
survival rate means after
diagnosis, after five years
how many patients are still alive,
and it looks actually
really good for stage zero,
100% of patients are still
alive after five years.
Stage one, 100% of
patients are still alive,
so you can really see that we
have made a lot of progress
in the recent years when
it comes to breast cancer,
and especially for the early stages,
diagnosis is so important
so everyone should always
get their mammograms
and their early check-ups
from their medical doctors.
As soon as the cancer starts to spread,
we actually see that the numbers drop,
so for stage two we have 93%,
for stage three 72%, so
the numbers are going down.
But now if you look to
metastatic breast cancer,
it actually drops to 20%,
so only 20% of patients
that have been diagnosed
with metastatic breast cancer
are still alive after five years,
and that's terrible of course.
And this is where we start our research.
So we specifically focus on
this group of breast cancer
patients that have metastasis,
and try to change these numbers,
and get them up, eventually,
hopefully to 100% as well.
Now of course you could argue,
that seems rather obvious
that we should help these patients,
what are we doing
differently in our research,
and I'll tell you about the
research at Cold Spring Harbor,
and why we think we have
a very new, very promising
approach to helping these patients.
So if we think of an
organism, like the human body,
you may have heard that
actually it is filled
with small tiny units called the cells,
and within the cells you have
something called chromosomes,
and these chromosomes are made of DNA.
Now DNA, this is our genes,
this is our inherited material,
whatever is passed down from
the parents to the children.
So this is what I'm talking about,
when I talk about genes are DNA.
Every cell in the body has that.
And for the last about 50 to 60 years,
scientists all around the world thought
that there is a very
simple, two-step process
of how a gene works in the body.
So you have DNA, a gene.
And in the first step,
it is converted into a
molecule that we call MRA.
And in the second step, it is a protein,
now proteins are generally the
functional parts in the cell,
they make the body run,
they do all of the functions in the body,
or so we thought until recently.
So this is what all of the scientists
for the last six years focused on,
and then in the last
say five to ten years,
we had some really cool, new technologies
that allowed us to find additional genes.
And now theses new genes,
they actually stop here at the first step.
So they don't make a protein ever,
they do not code for a protein,
hence we call them
non-coding RNAs or NCRNAs,
and they actually are
functional on this level,
they don't have to make the protein,
they're still very important
for the function of the cell.
Of course that's why we didn't
know that these existed,
no one has ever looked
into these molecules
and investigated them in the context
of any cancer for that matter.
So this is all very new science.
Now you may argue, well that sounds like
it's rather the exception from the rule.
Is this really important
for the human body?
So let me show you all the
genes in the human body, here.
And then red, all of the
ones that make protein,
and in blue, all the other
new ones that we found.
So two-thirds of all genes in
the human body are these new,
called non-coding RNA genes
that we didn't know they that existed.
So, we hope that somewhere
in these two-thirds of genes
that we haven't explored
yet, we'll find the answer,
not only for metastatic breast cancer,
but also to many other diseases.
This part of the genome
is also sometimes referred
to as the dark matter of the genome
because it's everywhere, it's a majority,
and we're not exactly
sure even what it does.
So you can see the
analogy there hopefully.
In our lab, we specifically
focus on something called
long non-coding RNAs and it
just means they are long.
So it's defined by length, totally easy.
We also called them lncRNAs,
and we have about 27%,
so one-quarter of the genome
are in these long non-coding RNA genes.
And this is where we in
our research comes in,
these are the molecules we
focus on in trying to find
a better, new treatment for
metastatic breast cancer.
So how do we do this?
You start counting that we have 16,000.
So quite a high number, of course.
And then we went through
16,000 molecules one by one,
with a computer obviously.
And tried to figure out
which of them are important
in metastatic breast cancer,
so the way we look at it is
we have a very low
level of these molecules
in a healthy breast, and in cancer,
you have a very, very high level.
So the idea is, let's
bring this high level down
to the level of a normal cell again,
and hope that this will
get rid of the tumor
and that's exactly what we do,
so how do we get those high levels down?
We actually destroy
these dark matter genes,
and I'll show you how to destroy them
in a short animation here.
Here in the middle is one example
for one of these non-coding
or dark matter genes.
And up here we developed a new drug
that we call antisense oligonucleotides,
doesn't really live in
occult at this point,
if anyone is interested
on how they work exactly.
Feel free to ask me about that later.
But at this point we have this new drug
that binds to our dark
matter gene, there it goes.
And now, it triggers a
mechanism in the cell.
That cuts this dark matter gene,
and that leads to a total destruction of
this dark matter gene.
It's now gone from the cell.
So that's great, we can get rid of them.
But what really happens to the
cancer if we get rid of them
And the first thing we do
whenever we test a new drug is
we go into a test dish
and test this in the lab.
And I'm sure that there's some
of colleague somewhere around
that can show you exactly what we do,
we use this model system
called organ lines,
so little mini tumors that we grow
and they're out there I hear,
they are over the building,
so if you are interested, go
over and have a look at them.
This is how one of
these organs looks like,
and now I hope you can
see it makes these arms,
it stretches in all directions,
and this is the bad thing about cancer,
it actually invades surrounding material,
it invades into the
bloodstream, into the brain,
into the liver, so that's
what we want to inhibit.
Now after drug treatment,
this is how they look,
so they completely lose their arms,
now since they lost these
arms, these protrusions,
they cannot invade anymore to the brain
or to the liver so that
was pretty exciting,
but this is in the dish,
so what happens if we put
it into a living organism,
and since we can't exactly
test this on humans right away,
the next closest model organism
that we use are mouse
models of breast cancer.
So what happens if we put into a mouse?
This graph illustrates what will happen,
so the black part up here would be mice
that have not received the drug
and in red we see mice
that have received the drug
and I hope you can appreciate
that even from the very first dose,
from the very first time,
there's a large difference
and we actually have only
half the amount of tumors
in the mice that have received the drug
versus the mice that didn't receive.
Now you would think, well
half is not exactly zero
and you're right but remember
this is early stage research
and we have only targeted
one out of 16,000 molecules
at this point so you could imagine
what happens if we combine
with a second or a third.
Now remember in the beginning,
I told you that the biggest problem
with breast cancer is metastasis,
so what happens if we give
this drug to our mice,
what happens to metastasis.
And we're excited to say that again,
black would be the untreated mice,
and in red, we have the treated mice.
So you actually have a 70% to 80%
reduction of metastasis in these mice.
And this is very, very
exciting for us here,
and generally if anyone in cancer research
gets a 70% or 80% reduction
this is really, really good.
So we are moving forwards,
hopefully soon to clinical trials.
And I will take my topic with me
and start my own laboratory next year,
that's exciting too.
And with that I just would like to thank
a number of people here,
I'm in the laboratory of Dr.
David Spector here on the left,
and you may have seen him
around, he has a poster as well.
I saw him explaining some
of the organ lines as well.
Obviously sieving through
these 16,000 targets
requires more than one person.
So this is all of them, who
were very helpful with that.
And we also received a number of funding
from both local organizations
like Stand up for Olympic cancer equipment
and also currently Susan G. Komen
and most of our funding
actually comes from the NIH,
so we should thank them as well.
And now I would like to
thank you for your attention
and I'm happy to take any questions.
(applause)
Yes?
- [Audience Member] Are there
any side effects to that drug
that you're giving to mice?
- I'm so glad you asked that question,
so in case you haven't heard,
she's asking if there's any
side effects to the drugs.
And that's one of the really
cool things about our approach,
they are developed in a way
that they only target cancer cells,
none of the healthy cells in the body.
So the hope would be that we
can reduce the side effects
that we currently get with
chemotherapeutics for example.
- [Audience Member] So the
ASO treatment basically stops
the cancer cells from spreading
but it doesn't get rid of the cells?
- Right, so the question was,
does the treatment stop
the cells from spreading
or does it completely
get rid of the tumor.
So it depends on which of
those 16,000 targets we target,
for some of them it only,
"only", still great.
It stops spreading, for others
it actually kills the cancer cells
and then you can combine them in a way
that you can get rid of the
tumor and of the metastasis.
Okay, I don't know who was first.
Okay, we start with yellow shirt.
- [Audience Member] For the drug that
would make the tumor stop,
how does it actually cut
and destroy the target?
- So how does the antisense
drug find its target?
So we are actually exploiting a mechanism
that is already in the cell,
so we're not introducing anything
that the cell didn't have.
So this small antisense oligonucleotides,
these new drugs they are
very specific binding
to the target of interest
that we designed it for.
And then this is like the antisense,
all it knows is a DNA molecule
and our dark matter is an RNA molecule,
and this DNA/RNA combination
is recognized by the cell,
so they're inside waiting in the cell for
exactly these kinds of
structures and destroys it.
And now we have blue shirt, sorry.
- [Audience Member] Well, in
the slides you looked at RNA,
is there any difference
between MRA and just RNA?
- Yes, so our friend
here in the front asked
if there's a difference
between MRA and RNA in general,
so RNA just means all
of the RNA molecules,
a subgroup is MRAs, and every
MRA molecule makes a protein
and then the other part
of these non-coding RNA
that don't make a protein.
But they are all from the chemistry,
they all belong to the big group of RNA.
- [Audience Member] Is
this only for metastatic
or can you use earlier on as
soon as you discover something?
- Great question, the
question was if you can use it
before it started to metastasize,
and we're currently
exploring that in the lab
if there's a benefit to giving it earlier
before metastasis has
started because that,
of course, would be fantastic,
if you could prevent metastasis
in a patient that has,
for example, only stage one tumors
and then will be treated with this drug
to prevent any spreading.
So we're currently investigating,
but the hope would be that eventually
we'll find something
that works for that too.
Okay, I'll try to remember the order,
I think you were first.
- [Audience Member] We've had
the human genome decoded for some time,
I'm wondering why we haven't
seen those non-coding RNA?
- Right, so why have we not
found those non-coding RNAs
in the human genome, we have actually,
but the Human genome
project was completed not
super long ago, and then it
took some time to understand
which parts of the genome
are actually transcribed
or processed into this RNA molecule
because it isn't the whole genome.
There are regions in a genome
that are just regulatory,
they don't make any RNAs whatsoever,
so we needed even more technologies,
even more experiments to figure out,
which ones make RNA
molecules in the first place.
Okay, I think there was
a question in the back.
There's too many questions,
okay I think you were first.
- [Audience Member] Okay, my question is
how long do you have to keep
the drug to get the effect?
So how long do you keep
the drug to see an effect,
that's something we're
currently still investigate
because we have a sonic clinical trial,
so I can't really say,
but there have been studies in mice
where you can up to 9 months
of stability in the body.
Okay, now we start with blue first.
- [Audience Member] How
do you get breast cancer
in the first place?
- How do you get breast
cancer in the first place?
That's a fantastic question
and there's a million answers to that,
so there's some people
that have a genetic
predisposition to breast cancer,
meaning it runs in their
family if that makes sense.
So if say, the mother,
and the grandfather,
and the aunt, and the
great-aunt, and the cousin
all have breast cancer,
there is the chance
that somewhere in your
genome there is a mutation
that you inherited as well,
that will eventually give you cancer.
But there's also a lot of
other factors, for example,
nutrition or obesity is a
big factor for breast cancer.
So if you're above a
certain body mass index
you have a higher risk
of getting breast cancer.
So it is generally, eat healthy, exercise,
and-- I'm wrapping up.
But it's a great question.
Okay, we have time for one more question.
- [Audience Member] Since
you discussed breast cancer
which is mostly for women,
is there work going on
into prostate cancer for men,
when are we gonna have
a discussion on that?
- We actually have tested some of our ASOs
in prostate cancer and the initial results
looks promising as well.
I think I have to wrap up at this point,
but I'll be around if anyone
has anymore questions.
Thank you so much.
(applause)
