October 30, 2023 • 22 mins
There's no doubt that medical research is accelerating – thanks to cutting-edge technology we can do experiments faster, at a bigger scale and crunch more data more efficiently. But today we're talking to Associate Professor Liz Caldon, who is slowing down her experiments to understand how we can better tackle cancer drug resistance.
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Episode Transcript
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Dr Viviane Richter (00:01):
There's no doubt that medical research is accelerating. Thanks to
cutting-edge technology, we can do experiments faster at a bigger
scale and crunch more data more efficiently. But today we're
talking to a cancer researcher who is slowing down her
experiments to understand how we can better tackle cancer drug resistance.
(00:22):
You're listening to Medical Minds. The podcast that takes you
inside the labs at the Garvan Institute of Medical Research.
I'm your host, Dr Viviane Richter. And with me here
is Associate Professor Liz Caldon, Head of the Replication and
Genome Stability Lab at Garvan. Welcome, Liz.
A/Prof Liz Caldon (00:41):
Thanks, Viv. It's wonderful to be here with you today.
Dr Viviane Richter (00:45):
Liz, I love science. Most people listening to this podcast love
science tell us, where did your love of science come from?
A/Prof Liz Caldon (00:53):
I've always loved science, but I also loved the arts,
and I loved reading. So when I went to university,
I actually undertook a double degree in science and law,
and I thought I'd end up in a career which
really incorporated both of those areas. And ultimately I did
do that for a little while. But while I was
at university, it was the science that really inspired me.
(01:16):
I loved being in the lab, performing experiments and not
really knowing what would be the outcome of those experiments
and also working in an area where there was a
bit of unknown. So when I did then go to
work in a law firm for a little while, I
worked in the area of intellectual property. I actually didn't
find that that really satisfied me because I was reading
(01:38):
about other people's experiments about their discoveries and reading about
the law that surrounded that. But I wasn't really at
the action end of finding out new ideas that could
actually change the face of medical research and humanity.
Dr Viviane Richter (01:53):
You wanted to make those discoveries yourself.
A/Prof Liz Caldon (01:55):
I did. I looked at what those discoveries were. I
was actually working on some law cases, which were about
the first devices for monitoring insulin for diabetics. And when
I looked at the science behind those discoveries, I was
so inspired.
Dr Viviane Richter (02:10):
Was there a point in your life where you realised
you wanted to be a medical researcher?
A/Prof Liz Caldon (02:15):
So ever since I've been little, I've had this scar
on my arm. It's a little round mottled scar, and
I never really understood what it was for. And then
when I was at university, I went to an amazing
presentation from the World Health Organisation. That was about smallpox
and the eradication of smallpox and I, it really clicked
to me then that that's what my scar was. It's
(02:37):
actually the vaccination mark for a smallpox vaccination, which I
received when I was a three year old. And what
I found particularly inspiring was it was through those vaccinations
and through those scars that the world has actually eradicated
the dreadful disease of smallpox. And that made me realise
the power of medical research and the power of medical
(03:00):
intervention that human beings can actually eradicate a whole disease.
And that was a really inspiring moment for me, where
I felt that medical research actually had the power to
change health for everybody.
Dr Viviane Richter (03:14):
Absolutely. A reminder of that would be the fact that
young people today don't have those scars. They don't need
that vaccine because we've eradicated that disease.
A/Prof Liz Caldon (03:23):
It is actually, um I mean, I now find it's also
a mark of my age, unfortunately, that I'm one of
those people who does have those scars, but it's very
satisfying now to see that my own children have not
had to receive that vaccine or are at risk of smallpox.
Dr Viviane Richter (03:38):
So, Liz, tell us about the first time you stepped
into a research lab.
A/Prof Liz Caldon (03:42):
The first research lab I went into was at university,
and my major was in microbiology, and I loved microbiology.
In microbiology it opened up a whole new world to
me of these tiny little organisms that we don't see
day to day. And there were many different projects we
did as part of microbiology labs. But one of the
(04:05):
ones that stood out to me was when we were
trying to grow bacteria that glowed in the dark. So
if you think about deep sea creatures, we often think
of that as a fluorescent environment. And in that environment,
creatures express these amazing little proteins, which can glow. They're
often called things like green fluorescent protein. And in one
(04:26):
of my first laboratories, we were trying to grow bacteria
that could express these proteins and actually glow. If we
walked into a dark room, we could see these glowing
plates of bacteria.
Dr Viviane Richter (04:36):
And do you still use that green fluorescent protein in
your research today?
A/Prof Liz Caldon (04:41):
Yes, it's amazing how many tools from nature we do
in fact use in our research. So if I take
the example of green fluorescent protein, or I'm gonna call
it GFP now, because that's what we call it in
the lab. If we're investigating cancer cells, what we will
do is we will make cancer cells produce this GFP,
and we can then grow those cancer cells in a
(05:02):
dish and look at them under the microscope. And when
they produce the GFP, we're able to visualise those cells
really effectively because they glow green. We can track the
way that they move from one place to another. We
can track the way they grow or proliferate, so every
time they split, their daughter cells will also produce this
(05:22):
GFP protein that allows us to examine the whole lifespan
of a cancer cell and track its movements.
Dr Viviane Richter (05:30):
So you started with green fluorescent protein in the lab.
Where did you go from there?
A/Prof Liz Caldon (05:35):
Following my undergraduate studies, I went on to do a
Master of Science at the University of Toronto in Canada,
and this was an amazing place to do further studies.
It's a real hub of research. While I was there.
I was studying some of the mechanisms in basic biology
learning how cells control their proliferation and what are the
(05:57):
intricate mechanisms they use to control proliferation.
Dr Viviane Richter (06:01):
And that's a process that often goes wrong in cancer.
Is that right?
A/Prof Liz Caldon (06:05):
It is so cancer is often seen as a disease
of uncontrolled proliferation. So normally in our body, every cell
will know its destiny. It knows that it's meant to
grow for a period of time, and then it's meant
to stop. But one of the main things that goes
wrong in cancer is that those cues to stop proliferation
(06:26):
or to stop cell growth are actually taken away. And
the studies I undertook at the University of Toronto were
really important for me when I returned to Australia to
start my PhD because I was studying that process of
proliferation and the loss of control of proliferation in breast cancer.
Dr Viviane Richter (06:45):
So we were lucky enough to have you come back
to Australia. Tell us about your research here.
A/Prof Liz Caldon (06:50):
When I came back to Australia, I was initially studying
proliferation in breast cancer cells and understanding some of the
basic mechanisms of how breast cancer cells grow and proliferate.
And what controls that. When we look at breast cancer
and how breast cancer actually develops, even though we think
of cancer as being a disease of uncontrolled proliferation, breast
(07:13):
cancers actually take a long time to develop. They can
take up to 10 years for a breast cancer to
be detected in the body or even longer. So even
while it's a disease of uncontrolled proliferation, some of that
growth is quite slow. So in my research, I became
particularly interested in understanding the differences between slow growth and
(07:34):
fast growth and how that impacted on cancer biology. And
the first thing that might pop into your mind is
that people die from the fast growing breast cancers. But
that's actually not the case. About 50% of breast cancer
deaths are actually from what we'd often characterise as a
slower growing breast cancer. And I think it's really important
(07:55):
to study that slow growth and understand its biology, because
by understanding the differences between those slow growing and fast
growing cancers, we actually start to understand that they need
different drugs. And for that reason we have been specifically
studying slow growing cancers in our lab and this means
(08:15):
our experiments can actually take a really long time. In fact,
some of our experiments take up to four years in length.
We're trying to really understand how these slow growing cancers
respond to drugs, but it's been a really important exercise
for us, and it's been extraordinarily fruitful in terms of
the results we've had from these long term experiments.
Dr Viviane Richter (08:37):
So what have you learned about breast cancer through your slow
growing cancer cell lines?
A/Prof Liz Caldon (08:43):
We've found by performing longer term experiments, we uncovered different
types of biology about cancer cells. Fast growing cells tend
to have a biology where they will take lots of
signals from their environment and use those signals as cues
to make them grow really, really fast. But with slow
(09:03):
growing cells, they actually use different cues from their environment.
These cues we use for the environment are often the
basis of the way we use drugs. We use drugs
that interrupt those signalling pathways in those cues. So if
we use drugs for fast growing cells, they won't necessarily
work on slow growing cells because those slow growing cells
(09:25):
rely on different pathways to stimulate their growth.
Dr Viviane Richter (09:28):
And so you're looking at cancer drug resistance is that right?
A/Prof Liz Caldon (09:32):
So the most common subtype of breast cancer is oestrogen
receptor positive breast cancer. It accounts for about 75% of
women with breast cancer. And with this disease, the majority
of these cancers are slow growing. Initially, a woman will
get surgery and perhaps chemotherapy for this type of cancer,
and following that, they'll receive anti-hormone therapy for a period
(09:56):
of 5 to 10 years. For those who are listening
who are familiar with this and because it's so incredibly common,
a number of you will be. These women receive drugs
with names like Tamoxifen or Arimidex. Now, while these drugs
are really successful in preventing a recurrence of breast cancer,
about 30% of women who get ER positive breast cancer in
(10:20):
fact get a recurrence of their breast cancer. And once
it comes back, it can be extremely difficult to treat.
It's understanding the disease of these women who get these
recurrent breast cancers after already having suffered through an initial
breast cancer.
Dr Viviane Richter (10:37):
So what have you found out about cancer recurrence?
A/Prof Liz Caldon (10:40):
So the reason that these cancers come back is because
of drug resistance. These cancer cells have an extraordinary ability
to adapt and change themselves so that they're able to
evade the drugs that we give them. And that's part
of what we study. We study how those cancer cells
evolve under the pressure of drugs over a period of
(11:02):
years and what changes happen in those cancer cells so
that they no longer respond to therapy.
Dr Viviane Richter (11:08):
So what are you seeing under the microscope when you're
looking at these drug-resistant cells?
A/Prof Liz Caldon (11:13):
We take these cells and we grow them in dishes
and expose them to drugs for a period of months.
And we might see that for these cells for the
first couple of months. We don't actually see any changes
in them, but as we keep observing them, we can
see with the passage of time that these cells start
to evolve and change and they manage to gain this
(11:37):
extraordinary ability to adapt to the drug. We can investigate
that at a number of different levels, and I'm very
lucky being located at the Garvan Institute. We have some
extraordinary technologies there which allow us to understand the changes
in these cells at a DNA level, a protein level,
and at a single cell level, looking at each cell
(11:58):
individually to understand how each cell differs to one another
in the way it changes in response to drugs.
Dr Viviane Richter (12:04):
So what have you learned about these changes to the
cancer cells?
A/Prof Liz Caldon (12:09):
We've actually learned that the change is not immediate and
that it goes in phases so cells can go through
a period of adaptation where they actually start to reprogram themselves.
And during that period of adaptation, they are not growing
particularly fast. They do not stand out. They're not the
(12:31):
kind of cell that you'd really see as the enemy.
In that state, they seem quite benign. But those adaptive
changes are really what's setting them up. To be able
to persist and grow through drugs as they further develop.
They're persistent. They're an unknown, something that can go underneath
(12:52):
the radar for a really long period of time.
Dr Viviane Richter (12:55):
So how is your research going to help patients with
breast cancer in the future?
A/Prof Liz Caldon (13:00):
At the moment, breast cancer is a disease that is
often not seen as the most serious of cancers. We've
got so many amazing treatments for breast cancer, and actually,
as a researcher, I find that really inspiring because a
lot of those treatment options have actually arisen from research.
(13:21):
But the problem with breast cancer is this high rate
of recurrence. And when patients recur, it is those patients
that we actually don't have a lot of treatment options for,
because a lot of the standard therapies don't work that
well on patients with recurrent disease. And in fact, that's
(13:41):
why I particularly study that disease. To try to understand
why those cancer cells won't respond to current therapies and
what new therapies we can develop to particularly target those
types of cancers. We're finding that those sorts of cancer
cells that are slow growing actually rely on different molecular
(14:03):
pathways to fast growing cells. They're actually doing different things
on the inside. So if we treat those cells with
the same sorts of drugs that we give to fast
growing cells, they're not going to work for that very
reason because they don't rely on those pathways. They're actually
relying on a different machinery to make themselves tick. So
our work is really about understanding that machinery, understanding what
(14:26):
makes a slow growing cell tick, and how can we
find the Achilles heel of those cells. At the moment,
there's a lot of uncertainty for people who are receiving
long term therapy for breast cancer to stop breast cancer recurrence.
Those survivors of an initial breast cancer are asking questions
such as
(14:48):
term therapy? Those long term therapies don't come without side effects.
In fact, they're quite debilitating side effects, some of them.
And we would love to be able to understand which
patients don't actually need to receive those long term therapies
to stop a breast cancer recurrence. For those patients who
do go on to get a recurrence, we want to
know how to treat them better. We want to be
(15:10):
able to offer a solution. If there is a cancer recurrence.
Dr Viviane Richter (15:14):
For patients that have breast cancer and are on these
long term therapies, what drugs do you think will benefit
them in future?
A/Prof Liz Caldon (15:23):
In the future? I think for breast cancer patients we'll
have much more personalised options at the moment for this
large number of women who do receive these preventative drugs.
And at the end of the day, this ends up
being something like one in 14 or one in 15
women in their lifetime. Because this type of breast cancer
(15:44):
is so extraordinarily common. If these women go on to
get a recurrence, I think we will be able to
offer them personalised therapy. We will be able to look
at their particular type of recurrent disease and analyse that
disease and understand better what is making that disease tick
and how to better treat them with drugs that are
specific for their particular recurrence?
Dr Viviane Richter (16:07):
What are patients with breast cancer telling you about their treatment?
A/Prof Liz Caldon (16:11):
Through my research, I'm lucky to interact with a number
of breast cancer patients in the field. We call breast
cancer patients who help out with research projects, we call
them consumers, or they call themselves consumers. This is a
group of wonderful women who advise me on my research
projects and how relevant they are for the breast cancer community.
(16:33):
And some of the most important feedback I've had from
that community is that there is a really big fear
of recurrence from breast cancer, and they really want better
options to understand how that recurrence will be dealt with.
If it in fact occurs.
Dr Viviane Richter (16:51):
It's that fear of the unknown, isn't it?
A/Prof Liz Caldon (16:54):
Absolutely so. After an initial breast cancer, women who are
on these drugs have that constant daily reminder of that
recurrence because they're in fact taking a preventative therapy for
a period of 5 to 10 years after that initial diagnosis.
And they're asking the question
It's giving me pretty horrible side effects. And is it
(17:17):
actually working? Is it actually doing its job? And will
I ever get a breast cancer recurrence? Ultimately, this is
the group of women that we're aiming to help, and
we would love to give them the confidence in their
daily lives that they know that the therapies that they
are taking are effective, that they know there are solutions
if they do get a recurrence. And that's what we
(17:39):
work towards in our laboratory.
Dr Viviane Richter (17:41):
Liz, you've been at Garvan for a long time. What
makes this such a world leading institute for cancer research?
A/Prof Liz Caldon (17:48):
The Garvan has some really incredible researchers who I am
lucky enough to call my colleagues, and there's expertise across
a large number of different cancers as well as other
types of disease. And it's really this brains trust that
helps me in my research. I've got amazing colleagues who
I can bounce ideas off and exchange ideas, collaborate on
(18:12):
experiments and together we are really working towards different and
better outcomes in cancer.
Dr Viviane Richter (18:19):
So this is all quite far from IP and patents.
We're glad we didn't lose you to your law career.
A/Prof Liz Caldon (18:26):
Yes, it's definitely a contrast to the desk job in
the law firm, but I've got to say it's a
path that I've really enjoyed over the last 20–25 years
since making that decision. Being in a laboratory and in
a laboratory setting has everyday challenges. And, of course, some
days aren't great. Some days everything doesn't work, But just
(18:47):
every now and then you just have that real light
bulb moment that is so inspiring. It is wonderful to
be there as we're breaking new ground in understanding cancer biology.
I also have an opportunity to work with many younger
people who are starting that research journey for themselves. I
supervise PhD students and they are just starting to uncover
(19:10):
how wonderful it is to be at the forefront of
research and making new discoveries.
Dr Viviane Richter (19:15):
Now, before we let you get back to the lab
and to your discoveries. It's time for the fast five.
What do you do in your downtime?
A/Prof Liz Caldon (19:23):
I've got to say, I don't get a lot of downtime.
I'm in the lab a lot. And in the rest
of my time, I spend with my family. So one
of the things I have been doing in my downtime
is I have been a netball team manager for one
of my daughters this year.
Dr Viviane Richter (19:39):
What's the most challenging thing you've ever had to do?
A/Prof Liz Caldon (19:41):
Well, a couple of years ago, I, for some reason
decided to take my kids abseiling for the first time. Wow.
And I thought because they loved climbing things, they'd be
right into it. And I wouldn't actually have to do
very much at the time. But unfortunately, they both got
quite scared. So I had to set the example by
(20:02):
being the first one over the side.
Dr Viviane Richter (20:05):
Oh, no
A/Prof Liz Caldon (20:05):
With a big smile on my face as well. So
that was rather challenging to overcome my fears while looking
happy about it as well.
Dr Viviane Richter (20:15):
Liz, do you have any secret skills?
A/Prof Liz Caldon (20:17):
Well, when I was in high school and at university,
I was in fact a fencer. So one of my
secret skills is a bit of skill with the foil. Now,
if you don't know what the foil is, there's three
weapons in fencing. There's the foil, the epee and the sabre,
and my specialty was the foil.
Dr Viviane Richter (20:35):
What's been your best holiday?
A/Prof Liz Caldon (20:37):
For my 30th birthday I did a camping trip in Kakadu,
and that was an absolute standout of a holiday. Just
getting to get off the beaten track and go and
see waterfalls with no one else around. Hopefully not run
into any crocodiles, of course, but it was an absolutely
stunning part of Australia.
Dr Viviane Richter (20:58):
Is there anyone you admire?
A/Prof Liz Caldon (21:00):
So there's a lot of people I admire. I admire
members of my family, a lot of my colleagues. There's
kind of no one person I kind of see as
an inspiration because there's so many inspirational people around me.
But this year's Nobel Prize for Medicine was awarded to
two individuals, and one of them was Katalin Kariko. And she's
(21:23):
a scientist who helped develop the mRNA vaccines, which are
being used for COVID. And she has an extraordinary life
story of how she followed her passion for science. She
didn't get supported along a lot of the way, but
she was so driven by her desire to understand this
biology that she persisted despite everything that happened to her.
Dr Viviane Richter (21:48):
Associate Professor Liz Caldon. Thank you so much for joining
us on Medical Minds.
A/Prof Liz Caldon (21:53):
It's been my absolute pleasure, Viv. I've really enjoyed telling
you about our research.
Dr Viviane Richter (21:58):
If you'd like to know more about Associate Professor Caldon's
research or the work we do at Garvan, head to garvan.org.au.
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter.
Thanks for listening. This podcast was recorded on the traditional
(22:20):
country of the Gadigal people of the Eora Nation. We
recognise their continuing connection to land, waters and community. We
pay our respects to Aboriginal and Torres Strait Islander cultures
and Elders past, present and emerging.
There's no doubt that medical research is accelerating. Thanks to
cutting-edge technology, we can do experiments faster at a bigger
scale and crunch more data more efficiently. But today we're
talking to a cancer researcher who is slowing down her
experiments to understand how we can better tackle cancer drug resistance.
(00:22):
You're listening to Medical Minds. The podcast that takes you
inside the labs at the Garvan Institute of Medical Research.
I'm your host, Dr Viviane Richter. And with me here
is Associate Professor Liz Caldon, Head of the Replication and
Genome Stability Lab at Garvan. Welcome, Liz.
A/Prof Liz Caldon (00:41):
Thanks, Viv. It's wonderful to be here with you today.
Dr Viviane Richter (00:45):
Liz, I love science. Most people listening to this podcast love
science tell us, where did your love of science come from?
A/Prof Liz Caldon (00:53):
I've always loved science, but I also loved the arts,
and I loved reading. So when I went to university,
I actually undertook a double degree in science and law,
and I thought I'd end up in a career which
really incorporated both of those areas. And ultimately I did
do that for a little while. But while I was
at university, it was the science that really inspired me.
(01:16):
I loved being in the lab, performing experiments and not
really knowing what would be the outcome of those experiments
and also working in an area where there was a
bit of unknown. So when I did then go to
work in a law firm for a little while, I
worked in the area of intellectual property. I actually didn't
find that that really satisfied me because I was reading
(01:38):
about other people's experiments about their discoveries and reading about
the law that surrounded that. But I wasn't really at
the action end of finding out new ideas that could
actually change the face of medical research and humanity.
Dr Viviane Richter (01:53):
You wanted to make those discoveries yourself.
A/Prof Liz Caldon (01:55):
I did. I looked at what those discoveries were. I
was actually working on some law cases, which were about
the first devices for monitoring insulin for diabetics. And when
I looked at the science behind those discoveries, I was
so inspired.
Dr Viviane Richter (02:10):
Was there a point in your life where you realised
you wanted to be a medical researcher?
A/Prof Liz Caldon (02:15):
So ever since I've been little, I've had this scar
on my arm. It's a little round mottled scar, and
I never really understood what it was for. And then
when I was at university, I went to an amazing
presentation from the World Health Organisation. That was about smallpox
and the eradication of smallpox and I, it really clicked
to me then that that's what my scar was. It's
(02:37):
actually the vaccination mark for a smallpox vaccination, which I
received when I was a three year old. And what
I found particularly inspiring was it was through those vaccinations
and through those scars that the world has actually eradicated
the dreadful disease of smallpox. And that made me realise
the power of medical research and the power of medical
(03:00):
intervention that human beings can actually eradicate a whole disease.
And that was a really inspiring moment for me, where
I felt that medical research actually had the power to
change health for everybody.
Dr Viviane Richter (03:14):
Absolutely. A reminder of that would be the fact that
young people today don't have those scars. They don't need
that vaccine because we've eradicated that disease.
A/Prof Liz Caldon (03:23):
It is actually, um I mean, I now find it's also
a mark of my age, unfortunately, that I'm one of
those people who does have those scars, but it's very
satisfying now to see that my own children have not
had to receive that vaccine or are at risk of smallpox.
Dr Viviane Richter (03:38):
So, Liz, tell us about the first time you stepped
into a research lab.
A/Prof Liz Caldon (03:42):
The first research lab I went into was at university,
and my major was in microbiology, and I loved microbiology.
In microbiology it opened up a whole new world to
me of these tiny little organisms that we don't see
day to day. And there were many different projects we
did as part of microbiology labs. But one of the
(04:05):
ones that stood out to me was when we were
trying to grow bacteria that glowed in the dark. So
if you think about deep sea creatures, we often think
of that as a fluorescent environment. And in that environment,
creatures express these amazing little proteins, which can glow. They're
often called things like green fluorescent protein. And in one
(04:26):
of my first laboratories, we were trying to grow bacteria
that could express these proteins and actually glow. If we
walked into a dark room, we could see these glowing
plates of bacteria.
Dr Viviane Richter (04:36):
And do you still use that green fluorescent protein in
your research today?
A/Prof Liz Caldon (04:41):
Yes, it's amazing how many tools from nature we do
in fact use in our research. So if I take
the example of green fluorescent protein, or I'm gonna call
it GFP now, because that's what we call it in
the lab. If we're investigating cancer cells, what we will
do is we will make cancer cells produce this GFP,
and we can then grow those cancer cells in a
(05:02):
dish and look at them under the microscope. And when
they produce the GFP, we're able to visualise those cells
really effectively because they glow green. We can track the
way that they move from one place to another. We
can track the way they grow or proliferate, so every
time they split, their daughter cells will also produce this
(05:22):
GFP protein that allows us to examine the whole lifespan
of a cancer cell and track its movements.
Dr Viviane Richter (05:30):
So you started with green fluorescent protein in the lab.
Where did you go from there?
A/Prof Liz Caldon (05:35):
Following my undergraduate studies, I went on to do a
Master of Science at the University of Toronto in Canada,
and this was an amazing place to do further studies.
It's a real hub of research. While I was there.
I was studying some of the mechanisms in basic biology
learning how cells control their proliferation and what are the
(05:57):
intricate mechanisms they use to control proliferation.
Dr Viviane Richter (06:01):
And that's a process that often goes wrong in cancer.
Is that right?
A/Prof Liz Caldon (06:05):
It is so cancer is often seen as a disease
of uncontrolled proliferation. So normally in our body, every cell
will know its destiny. It knows that it's meant to
grow for a period of time, and then it's meant
to stop. But one of the main things that goes
wrong in cancer is that those cues to stop proliferation
(06:26):
or to stop cell growth are actually taken away. And
the studies I undertook at the University of Toronto were
really important for me when I returned to Australia to
start my PhD because I was studying that process of
proliferation and the loss of control of proliferation in breast cancer.
Dr Viviane Richter (06:45):
So we were lucky enough to have you come back
to Australia. Tell us about your research here.
A/Prof Liz Caldon (06:50):
When I came back to Australia, I was initially studying
proliferation in breast cancer cells and understanding some of the
basic mechanisms of how breast cancer cells grow and proliferate.
And what controls that. When we look at breast cancer
and how breast cancer actually develops, even though we think
of cancer as being a disease of uncontrolled proliferation, breast
(07:13):
cancers actually take a long time to develop. They can
take up to 10 years for a breast cancer to
be detected in the body or even longer. So even
while it's a disease of uncontrolled proliferation, some of that
growth is quite slow. So in my research, I became
particularly interested in understanding the differences between slow growth and
(07:34):
fast growth and how that impacted on cancer biology. And
the first thing that might pop into your mind is
that people die from the fast growing breast cancers. But
that's actually not the case. About 50% of breast cancer
deaths are actually from what we'd often characterise as a
slower growing breast cancer. And I think it's really important
(07:55):
to study that slow growth and understand its biology, because
by understanding the differences between those slow growing and fast
growing cancers, we actually start to understand that they need
different drugs. And for that reason we have been specifically
studying slow growing cancers in our lab and this means
(08:15):
our experiments can actually take a really long time. In fact,
some of our experiments take up to four years in length.
We're trying to really understand how these slow growing cancers
respond to drugs, but it's been a really important exercise
for us, and it's been extraordinarily fruitful in terms of
the results we've had from these long term experiments.
Dr Viviane Richter (08:37):
So what have you learned about breast cancer through your slow
growing cancer cell lines?
A/Prof Liz Caldon (08:43):
We've found by performing longer term experiments, we uncovered different
types of biology about cancer cells. Fast growing cells tend
to have a biology where they will take lots of
signals from their environment and use those signals as cues
to make them grow really, really fast. But with slow
(09:03):
growing cells, they actually use different cues from their environment.
These cues we use for the environment are often the
basis of the way we use drugs. We use drugs
that interrupt those signalling pathways in those cues. So if
we use drugs for fast growing cells, they won't necessarily
work on slow growing cells because those slow growing cells
(09:25):
rely on different pathways to stimulate their growth.
Dr Viviane Richter (09:28):
And so you're looking at cancer drug resistance is that right?
A/Prof Liz Caldon (09:32):
So the most common subtype of breast cancer is oestrogen
receptor positive breast cancer. It accounts for about 75% of
women with breast cancer. And with this disease, the majority
of these cancers are slow growing. Initially, a woman will
get surgery and perhaps chemotherapy for this type of cancer,
and following that, they'll receive anti-hormone therapy for a period
(09:56):
of 5 to 10 years. For those who are listening
who are familiar with this and because it's so incredibly common,
a number of you will be. These women receive drugs
with names like Tamoxifen or Arimidex. Now, while these drugs
are really successful in preventing a recurrence of breast cancer,
about 30% of women who get ER positive breast cancer in
(10:20):
fact get a recurrence of their breast cancer. And once
it comes back, it can be extremely difficult to treat.
It's understanding the disease of these women who get these
recurrent breast cancers after already having suffered through an initial
breast cancer.
Dr Viviane Richter (10:37):
So what have you found out about cancer recurrence?
A/Prof Liz Caldon (10:40):
So the reason that these cancers come back is because
of drug resistance. These cancer cells have an extraordinary ability
to adapt and change themselves so that they're able to
evade the drugs that we give them. And that's part
of what we study. We study how those cancer cells
evolve under the pressure of drugs over a period of
(11:02):
years and what changes happen in those cancer cells so
that they no longer respond to therapy.
Dr Viviane Richter (11:08):
So what are you seeing under the microscope when you're
looking at these drug-resistant cells?
A/Prof Liz Caldon (11:13):
We take these cells and we grow them in dishes
and expose them to drugs for a period of months.
And we might see that for these cells for the
first couple of months. We don't actually see any changes
in them, but as we keep observing them, we can
see with the passage of time that these cells start
to evolve and change and they manage to gain this
(11:37):
extraordinary ability to adapt to the drug. We can investigate
that at a number of different levels, and I'm very
lucky being located at the Garvan Institute. We have some
extraordinary technologies there which allow us to understand the changes
in these cells at a DNA level, a protein level,
and at a single cell level, looking at each cell
(11:58):
individually to understand how each cell differs to one another
in the way it changes in response to drugs.
Dr Viviane Richter (12:04):
So what have you learned about these changes to the
cancer cells?
A/Prof Liz Caldon (12:09):
We've actually learned that the change is not immediate and
that it goes in phases so cells can go through
a period of adaptation where they actually start to reprogram themselves.
And during that period of adaptation, they are not growing
particularly fast. They do not stand out. They're not the
(12:31):
kind of cell that you'd really see as the enemy.
In that state, they seem quite benign. But those adaptive
changes are really what's setting them up. To be able
to persist and grow through drugs as they further develop.
They're persistent. They're an unknown, something that can go underneath
(12:52):
the radar for a really long period of time.
Dr Viviane Richter (12:55):
So how is your research going to help patients with
breast cancer in the future?
A/Prof Liz Caldon (13:00):
At the moment, breast cancer is a disease that is
often not seen as the most serious of cancers. We've
got so many amazing treatments for breast cancer, and actually,
as a researcher, I find that really inspiring because a
lot of those treatment options have actually arisen from research.
(13:21):
But the problem with breast cancer is this high rate
of recurrence. And when patients recur, it is those patients
that we actually don't have a lot of treatment options for,
because a lot of the standard therapies don't work that
well on patients with recurrent disease. And in fact, that's
(13:41):
why I particularly study that disease. To try to understand
why those cancer cells won't respond to current therapies and
what new therapies we can develop to particularly target those
types of cancers. We're finding that those sorts of cancer
cells that are slow growing actually rely on different molecular
(14:03):
pathways to fast growing cells. They're actually doing different things
on the inside. So if we treat those cells with
the same sorts of drugs that we give to fast
growing cells, they're not going to work for that very
reason because they don't rely on those pathways. They're actually
relying on a different machinery to make themselves tick. So
our work is really about understanding that machinery, understanding what
(14:26):
makes a slow growing cell tick, and how can we
find the Achilles heel of those cells. At the moment,
there's a lot of uncertainty for people who are receiving
long term therapy for breast cancer to stop breast cancer recurrence.
Those survivors of an initial breast cancer are asking questions
such as
(14:48):
term therapy? Those long term therapies don't come without side effects.
In fact, they're quite debilitating side effects, some of them.
And we would love to be able to understand which
patients don't actually need to receive those long term therapies
to stop a breast cancer recurrence. For those patients who
do go on to get a recurrence, we want to
know how to treat them better. We want to be
(15:10):
able to offer a solution. If there is a cancer recurrence.
Dr Viviane Richter (15:14):
For patients that have breast cancer and are on these
long term therapies, what drugs do you think will benefit
them in future?
A/Prof Liz Caldon (15:23):
In the future? I think for breast cancer patients we'll
have much more personalised options at the moment for this
large number of women who do receive these preventative drugs.
And at the end of the day, this ends up
being something like one in 14 or one in 15
women in their lifetime. Because this type of breast cancer
(15:44):
is so extraordinarily common. If these women go on to
get a recurrence, I think we will be able to
offer them personalised therapy. We will be able to look
at their particular type of recurrent disease and analyse that
disease and understand better what is making that disease tick
and how to better treat them with drugs that are
specific for their particular recurrence?
Dr Viviane Richter (16:07):
What are patients with breast cancer telling you about their treatment?
A/Prof Liz Caldon (16:11):
Through my research, I'm lucky to interact with a number
of breast cancer patients in the field. We call breast
cancer patients who help out with research projects, we call
them consumers, or they call themselves consumers. This is a
group of wonderful women who advise me on my research
projects and how relevant they are for the breast cancer community.
(16:33):
And some of the most important feedback I've had from
that community is that there is a really big fear
of recurrence from breast cancer, and they really want better
options to understand how that recurrence will be dealt with.
If it in fact occurs.
Dr Viviane Richter (16:51):
It's that fear of the unknown, isn't it?
A/Prof Liz Caldon (16:54):
Absolutely so. After an initial breast cancer, women who are
on these drugs have that constant daily reminder of that
recurrence because they're in fact taking a preventative therapy for
a period of 5 to 10 years after that initial diagnosis.
And they're asking the question
It's giving me pretty horrible side effects. And is it
(17:17):
actually working? Is it actually doing its job? And will
I ever get a breast cancer recurrence? Ultimately, this is
the group of women that we're aiming to help, and
we would love to give them the confidence in their
daily lives that they know that the therapies that they
are taking are effective, that they know there are solutions
if they do get a recurrence. And that's what we
(17:39):
work towards in our laboratory.
Dr Viviane Richter (17:41):
Liz, you've been at Garvan for a long time. What
makes this such a world leading institute for cancer research?
A/Prof Liz Caldon (17:48):
The Garvan has some really incredible researchers who I am
lucky enough to call my colleagues, and there's expertise across
a large number of different cancers as well as other
types of disease. And it's really this brains trust that
helps me in my research. I've got amazing colleagues who
I can bounce ideas off and exchange ideas, collaborate on
(18:12):
experiments and together we are really working towards different and
better outcomes in cancer.
Dr Viviane Richter (18:19):
So this is all quite far from IP and patents.
We're glad we didn't lose you to your law career.
A/Prof Liz Caldon (18:26):
Yes, it's definitely a contrast to the desk job in
the law firm, but I've got to say it's a
path that I've really enjoyed over the last 20–25 years
since making that decision. Being in a laboratory and in
a laboratory setting has everyday challenges. And, of course, some
days aren't great. Some days everything doesn't work, But just
(18:47):
every now and then you just have that real light
bulb moment that is so inspiring. It is wonderful to
be there as we're breaking new ground in understanding cancer biology.
I also have an opportunity to work with many younger
people who are starting that research journey for themselves. I
supervise PhD students and they are just starting to uncover
(19:10):
how wonderful it is to be at the forefront of
research and making new discoveries.
Dr Viviane Richter (19:15):
Now, before we let you get back to the lab
and to your discoveries. It's time for the fast five.
What do you do in your downtime?
A/Prof Liz Caldon (19:23):
I've got to say, I don't get a lot of downtime.
I'm in the lab a lot. And in the rest
of my time, I spend with my family. So one
of the things I have been doing in my downtime
is I have been a netball team manager for one
of my daughters this year.
Dr Viviane Richter (19:39):
What's the most challenging thing you've ever had to do?
A/Prof Liz Caldon (19:41):
Well, a couple of years ago, I, for some reason
decided to take my kids abseiling for the first time. Wow.
And I thought because they loved climbing things, they'd be
right into it. And I wouldn't actually have to do
very much at the time. But unfortunately, they both got
quite scared. So I had to set the example by
(20:02):
being the first one over the side.
Dr Viviane Richter (20:05):
Oh, no
A/Prof Liz Caldon (20:05):
With a big smile on my face as well. So
that was rather challenging to overcome my fears while looking
happy about it as well.
Dr Viviane Richter (20:15):
Liz, do you have any secret skills?
A/Prof Liz Caldon (20:17):
Well, when I was in high school and at university,
I was in fact a fencer. So one of my
secret skills is a bit of skill with the foil. Now,
if you don't know what the foil is, there's three
weapons in fencing. There's the foil, the epee and the sabre,
and my specialty was the foil.
Dr Viviane Richter (20:35):
What's been your best holiday?
A/Prof Liz Caldon (20:37):
For my 30th birthday I did a camping trip in Kakadu,
and that was an absolute standout of a holiday. Just
getting to get off the beaten track and go and
see waterfalls with no one else around. Hopefully not run
into any crocodiles, of course, but it was an absolutely
stunning part of Australia.
Dr Viviane Richter (20:58):
Is there anyone you admire?
A/Prof Liz Caldon (21:00):
So there's a lot of people I admire. I admire
members of my family, a lot of my colleagues. There's
kind of no one person I kind of see as
an inspiration because there's so many inspirational people around me.
But this year's Nobel Prize for Medicine was awarded to
two individuals, and one of them was Katalin Kariko. And she's
(21:23):
a scientist who helped develop the mRNA vaccines, which are
being used for COVID. And she has an extraordinary life
story of how she followed her passion for science. She
didn't get supported along a lot of the way, but
she was so driven by her desire to understand this
biology that she persisted despite everything that happened to her.
Dr Viviane Richter (21:48):
Associate Professor Liz Caldon. Thank you so much for joining
us on Medical Minds.
A/Prof Liz Caldon (21:53):
It's been my absolute pleasure, Viv. I've really enjoyed telling
you about our research.
Dr Viviane Richter (21:58):
If you'd like to know more about Associate Professor Caldon's
research or the work we do at Garvan, head to garvan.org.au.
And if you've enjoyed this podcast, please leave a review
and share with other podcast lovers. I'm Dr Viviane Richter.
Thanks for listening. This podcast was recorded on the traditional
(22:20):
country of the Gadigal people of the Eora Nation. We
recognise their continuing connection to land, waters and community. We
pay our respects to Aboriginal and Torres Strait Islander cultures
and Elders past, present and emerging.
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