October 17, 2024 • 31 mins
The human body has an incredible capacity to heal itself – whether it’s a paper cut, a broken bone, or your lungs recovering after a chest infection. But not all types of healing are good for us. Cancers seem to have hijacked the healing process to protect themselves from treatments and to spread more easily around the body. In this episode, we speak to Associate Professor Thomas Cox, who is working to put a stop to this and make existing cancer therapy more effective.
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Episode Transcript
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Dr Viviane Richter (00:01):
The human body has an incredible capacity to heal itself,
whether it's a paper cut, a broken bone or your
lungs recovering after a chest infection. But not all types
of healing are good for us. Some cancers have hijacked
the healing process to protect themselves from treatments. In today's episode,
(00:21):
we speak to a researcher who will explain how cancers
do this and how his research is paving the way
for better outcomes for patients. 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 Thomas Cox, head
(00:42):
of the Matrix and Metastasis Lab at Garvan. Welcome, Tom.
Associate Professor Thomas Cox (00:46):
Thanks, Viv. Great to be here.
Dr Viviane Richter (00:48):
Tom, where did this idea come from that cancers and
wound healing are linked?
Associate Professor Thomas Cox (00:54):
So, I think a lot of the early work studying
cancer was by pathologists. So, similar to what they do today.
Looking at the tumours under the microscope and trying to
piece together how they're different and why they might be different.
Some of this goes back really to the 1800s where
the pathologists could see that a cancer wasn't just made
(01:18):
up of cancer cells. There was a structure, you know,
around it that was holding those cells into place. And
that structure is very much the same as what we
see in our normal tissues and normal organs. If we
think about the heart tissue or we think about muscle tissue,
we have heart cells but they're held together by a
glue or a scaffold that gives them the shape of
the heart. And so what pathologists had noticed was actually
(01:42):
that this scaffold, this matrix, as we call it, was changing.
It appeared very different, and it was resembling some of
the properties that they could see in wound healing and
in scarring, for example. And so that really kicked off
this idea that you have both a sort of cellular component,
the the tumour cells, but also this extracellular sort of
(02:05):
outside of the cell, and they work together. And then
I guess, a few years down the line, this this
concept started to be refined, the idea that well, when
we think about normal wound healing, so if you or
I cut ourselves or injure ourselves in some way, the
body switches on these incredibly powerful programmes that have to repair.
(02:26):
They have to restore the normal tissue. And what happens
in cancer was that the cancer cells are sort of
activating those similar wound healing processes. And what this results
in really is this sort of idea of a a
healing or wound healing in and around the tumour. But
if we think about normal situations, we think about what
happens when you cut yourself or you break a leg.
(02:48):
That event has finished, and so the body heals. Normally,
it restores that tissue back to its normal status. But
in a cancer, the tumour is still there. And so
what we get is this sort of continual insult to
that tissue. So the the programme is switched on, but
it's never switched off. And this is something that we
(03:09):
do see in other diseases as well. We think about,
for example, lung fibrosis. Or we could think about liver
fibrosis where there's an insult. For example, it could be
smoking or drinking. If you continue to do that, then
this tissue has to continually repair. And what that leads
to is a tissue fibrosis. So, it's exactly the same
(03:30):
as what's happening in cancer is, this body's repair mechanism
is inadvertently essentially feeding into the progression of the tumour.
Dr Viviane Richter (03:40):
What does fibrosis look like? How can we visualise fibrosis?
Associate Professor Thomas Cox (03:45):
So, our understanding of fibrosis is essentially that tissue repair
process that has gone wrong or is not completing its
its programme as it should. The easiest way for you
and I to to think about it, or even to
see that would be scarring. So if we cut ourselves,
(04:06):
if we leave it alone, it would hopefully heal without
a scar. But of course, in some cases it doesn't.
Children are great. They keep picking at them whilst they heal.
And it's that repeated sort of injury. And what you
then get is this scar tissue, and it's it's made
up of this large amount of extracellular matrix, and we
see that we see this sort of white line. And
(04:29):
so that's what we get really in in tumours is
this scarring that forms in and around the tumour. And actually,
that's quite important because very early on, one of the
ways that tumours are diagnosed is there's a lump. There's
something there that wasn't there before, and that's a combination
(04:51):
of both tumour cells, which are expanding, obviously tumour cells
sort of uncontrollably divide, but also some of that fibrosis
that is forming this hard lump. And that's that's often
what you can feel as an individual. And obviously the
doctors would be the first sign that they maybe need
further tests.
Dr Viviane Richter (05:08):
So, what do we know about fibrosis now? Are there
some cancers that are more fibrotic than others? Or is
this potentially the key to a breakthrough for all cancers?
Associate Professor Thomas Cox (05:20):
So, what we know now and and I think, have
done over the last sort of four or five decades,
is begun to really start to understand the biology of
this fibrosis. Why is it important? How does it feed
into the progression of a cancer? And, more importantly, how
might that affect treatments that we give patients? Most cancers,
(05:42):
in fact all solid cancers, when we think about a
solid tumour versus a blood tumour which will have a
matrix will have this fibrotic kind of scar tissue, some
are much, much more fibrotic than others. A good example
of that would be pancreatic cancer, for example, and what
we've begun to understand is the context is incredibly important. So,
(06:08):
the tumour cells within that tumour and within the context
of that fibrosis, that fibrosis is having a huge path
now in how fast they divide, whether or not they
move and spread around the body in the process that
we call metastasis, whether they respond to a particular treatment
or not. And so, what we're starting to do is
(06:29):
think about designing therapies that are not just targeting cancer cells.
What we want to do is to target both the
cancer cells and this support network, or this fibrotic mass,
that forms around them. And in doing so, we now
treat the whole tumour rather than just the cancer cells.
And it's not just that it might be telling a
(06:51):
cancer cell to divide more. It also forms a bit
of a physical barrier sometimes. We think about scar tissue,
it's obviously it's a very dense tissue that can have
an effect of stopping some therapies from getting in as well,
and so part of that is about stopping the fibrosis
from forming. But I think we have to be very careful.
We have to do this in a bit of a
(07:12):
nuanced manner. And the reason I say that was because
a few years ago there was this sort of idea
that, well, if this fibrosis is bad, then well, surely if we
if we just get rid of it, then we will
effectively improve the outcomes in cancer. But what they realised
was you can't just get rid of everything. And we
(07:34):
think back to to what I mentioned earlier about how
all of our tissues in our body have these this matrix,
this tissue sort of structure. That actually is very powerful
in the normal situation of telling the cells what to do. So,
the reason our heart tissue just doesn't continue to get
bigger and bigger is because that tissue structure is saying no,
(07:55):
you're at the right size, now we carry out the function. So,
what we want to do is, rather than get rid
of that fibrosis, is look at how do we either
identify the really what we call pro-tumorigenic parts of it,
or effectively normalise it. So, let's say return it back
to what it should be and ultimately try to close
(08:16):
that loop of that repair mechanism. And in doing so,
I think we're going to be much, much more effective
and essentially improve the efficacy of our already approved standard
of care therapies. And so that's really the goal, I think.
Dr Viviane Richter (08:30):
Are there any particular cancers you're focusing on?
Associate Professor Thomas Cox (08:33):
So, we focus primarily in the pancreatic cancer, breast cancer
and lung cancer space. There's a lot of overlap in
some of these mechanisms when we talk about this tumour fibrosis,
whilst even though the tumours themselves are quite different. And
so we have a number of programmes of work which
are essentially trying to understand both those similarities, but also
(08:56):
those differences, and so can we learn from one type
of tumour and apply it to another. But this is
also important because when you think about a lot of cancers,
they spread around the body, uh, and this process of
metastasis that makes it very difficult to treat. And so
if we think about breast cancer, for example, one of
the common sites it spreads to is the lung tissue.
(09:18):
And so, actually, by studying across multiple cancers and looking
at the tissues, whether it's a primary lung cancer or
a metastatic breast cancer that's gone to the lung, we
can also start thinking about how we might treat these
different tumours based on the organ that they are within,
or based on the tissue remodelling programmes that they activate.
Dr Viviane Richter (09:39):
Why is it so critical to target fibrosis in these
cancers in particular? What is the limitation of current treatments?
Associate Professor Thomas Cox (09:49):
If we take pancreatic cancer as an example, this is
a very fibrotic tumour. Sometimes over 50% of the actual
tumour itself might be this scar tissue. And so effectively,
if we only target cancer cells, we may only be
targeting half of that tumour. But as I mentioned before,
(10:09):
one of the things this scar tissue, this matrix, can
do is blunt the efficacy of therapies that we're giving,
be this a chemotherapy, radiotherapy, even the new immunotherapies.
Dr Viviane Richter (10:21):
Like a physical barrier.
Associate Professor Thomas Cox (10:23):
Yes. And what we've started to realise is that as
we give a therapy, and this is some of the
work from my team, one of the things that happens
is you actually cause damage to the tumour, which is
that actually the therapy doing what it should do. But
of course, that damage, that killing of those cancer cells,
(10:43):
then sort of hyperactivates the body's wound healing response because
there's obviously damage that now needs to be effectively repaired.
And so sometimes your therapies do their job at killing
cancer cells. But one of the, I guess, side effects
is to trigger more of that fibrotic tissue to be deposited.
So this may mean that the tumour goes from 50%
(11:05):
to 60% to 70% and this becomes a problem because
that can stop the successive rounds of therapy getting into
the tumour. It may protect those cancer cells from other,
for example, immune cells. If we think about the context
of immune therapy, which is a new therapy that's been
coming out, and so the idea is, if we can
(11:25):
block that fibrosis at the same time as our therapy,
do we then essentially allow our therapy to continue to
carry its job out effectively? So, another problematic aspect of
this tumour fibrosis is when we come to monitoring patient
response to a particular therapy, especially for tumours that may
(11:47):
be deep inside the body, such as within the pancreas.
And this is because, typically, we may use an imaging
modality or approach like a CT. We hear about CT scans and
what they're doing is they're using these to monitor the
size of the tumour as we give a therapy. And
in many tumours we see the shrinking of that tumour.
(12:09):
And so this is an indicator that we're getting a response.
But in some pancreatic cancer patients and other fibrotic tumours,
what we actually see is that fibrosis replaces where those
cancer cells have been killed. And this means that effectively,
the tumour doesn't look like it's actually shrinking, and so
(12:32):
it can make it very difficult to stage a a
tumour and therefore to determine how effective that treatment might be.
And this is where we get that increase going up from,
you know, 60% or above. And it's not until surgery
and the tumour perhaps comes out that you can then
look at it and say, well, actually, it's mostly just fibrosis now.
(12:54):
The cancer cells have been killed, but it can make
it tricky.
Dr Viviane Richter (12:58):
Tell us what you're hoping to achieve through your research.
Associate Professor Thomas Cox (13:01):
One of the key things we're interested in is understanding
how do all of those building blocks of fibrosis come together?
How do they assemble and and how does that you
know scar tissue form within the tumour. So we've got
quite a large programme of work where we're targeting different
elements of that to try and block that. And the
(13:22):
idea behind that is that if we can prevent or
slow down that formation of that fibrotic tissue, that scarring
within the tumour, whilst we're giving our chemotherapy, then we
effectively make chemotherapy better and therefore hopefully improve the response
of that patient and therefore outcome. We've taken a number
(13:44):
of different approaches to doing this. A lot of what
we do partners with industry and biotech and pharma to
try to develop novel approaches. So, chemotherapy has been around
for for decades. It's tried and tested but this, these
anti-stromal therapies that I mentioned, these anti-fibrotics are very new
(14:06):
to the field of cancer. And so, by combining the two,
we're hoping to show that we can improve outcome in patients.
Dr Viviane Richter (14:14):
So, how do these treatments work? Because I would imagine
that you'd want to not turn off all healing, all
wound healing in the body, so you wouldn't want to
prevent all of fibrosis from happening, I would assume. How
do you specifically target this in a cancer?
Associate Professor Thomas Cox (14:31):
So, what we do in our different cancer models is
we look for things that have been activated in tumours.
If you remember back at the beginning of our chat,
when we were talking about how when we cut ourselves,
the body switches on these repair pathways - very powerful programmes
that are designed to repair the body quickly and then
(14:52):
they switch them off. But in cancers they've obviously switched
on and stay on. And so what we do is
look for those that are switched on and that allows
us to target those specifically. That means that, ultimately, if
a patient's on an anti-fibrotic therapy whilst they have the
tumour in their chemotherapy, then we'll be effectively targeting just that.
(15:13):
Of course, one of the things we will need to
do in the future is to ensure that, if you
were to cut yourself at the same time, that there
weren't going to be adverse effects. But that's obviously something
which we would be doing at that point of clinical translation.
Dr Viviane Richter (15:28):
Where is your research up to now?
Associate Professor Thomas Cox (15:31):
So, at the moment, we are at what we call
the sort of preclinical to clinical translation. So, what that
means is we have been working for a number of
years now with a Sydney-based pharmaceutical called Syntara working through
different generations of small molecule drugs, anti-fibrotics. And so the
(15:52):
idea is that we are showing that they work in
the Petri dish, as you would expect in a lab,
but then transition that into some of our models of
pancreatic cancer, in particular some of our mass models. And
last year we published some research showing that they work
in mass models of pancreatic cancer in combination with a
(16:16):
standard of care chemotherapy. And we see that we get,
and this is a pancreatic cancer model, so we see that
we get a decrease in that fibrosis within those tumours.
This actually leads to a slower growth of those tumours. So,
we've removed this fibrotic signal that's activating cancer cells to grow faster.
(16:37):
We actually saw that it spreads less around the body,
which is very, very important because metastasis is one of
the most complicated and difficult things to treat in patients.
So today, actually, this drug has been tried in what
we call phase one trials, which is to make sure
that the drug still has its same effects within people,
(17:02):
and a trial has been launched in a slightly different
type of cancer called myelofibrosis. This is a fibrotic bone
marrow cancer, if we can call it that. And so
the next step for us is to launch a phase
what we call 1c or 2a trial in pancreatic cancer. Uh,
(17:23):
and the idea of that is to run that at
the Garvan and the Kinghorn Cancer Centre in connection with
our clinical partners across Sydney and Australia. And so the
first thing we've got to do is check whether or
not our new anti-fibrotic drug is going to be safe
to give with chemotherapy. And then, once we're happy that
(17:43):
it's not going to negatively affect the efficacy of chemotherapy,
ask the question of whether or not it improves the
effects of chemotherapy. And so that's really where we're sort
of poised. We are hoping to launch that in 2025.
Dr Viviane Richter (18:01):
Tom, how does it feel to be on the cusp
of launching this clinical trial, which could potentially have a
significant impact for patients?
Associate Professor Thomas Cox (18:10):
So, it's a really exciting time right now. Obviously, a
lot of the work we've been doing is very much
understanding the biology of pancreatic cancer. As we know, it's
got in a terrible survival rate at the moment. Unfortunately,
it's less than 10%. A lot of that is because
there aren't that many effective therapies. Uh, and we really
(18:32):
do need to come up with new ways and new
combinations to, you know, shift that dial to really improve that.
And so this is a a really unique opportunity, I think.
This idea of anti-fibrotics or anti-stromal therapies, as we call them,
is still quite new in the field. There have been
a few trials out there with mixed results because we're
(18:57):
still learning about how that fibrosis scarring feeds into the cancer.
How that might complement, for example, chemotherapy. And at the moment,
from where we're sitting, we've got an incredibly strong signal,
like it's very exciting for us to see this route
to the clinic. And I guess from a personal perspective,
(19:20):
I'm a scientist by training. I I'm one of those people,
I like to understand how things work, but also why
they aren't working. Why are they not doing what they
should be doing and which is obviously what happens in cancer.
And so this idea that we can now take all
that biology, all that understanding that we've generated and the
(19:43):
proof of principle, and transition that through to a potential
therapeutic that may have beneficial effects. I think it would
be hugely rewarding to see a trial kick off that
would pale in comparison if it made a difference to
just a single patient. I would honestly feel that after
(20:04):
about 15 years of, of working in this space almost
on this project, that to see that benefit, even a
single patient would be enormous.
Dr Viviane Richter (20:13):
So, what are you hoping to see from this clinical trial?
Associate Professor Thomas Cox (20:17):
So, the first thing I mentioned we'll be looking into
confirming safety. So, we know that this drug itself is
safe to give to people. But we also need to
make sure that, when given at the same time as chemotherapy,
we don't make any of those classical side effects of chemotherapy.
We don't want to make them worse. And we certainly
don't want to decrease the efficacy of chemotherapy that we
(20:40):
currently have. So, the first is safety. The second is
then efficacy to ensure that it is doing that having
that antifibrotic role and that that is then improving the
response that patients have to chemotherapy.
Dr Viviane Richter (20:54):
In this clinical trial, what would be the best possible
outcome for patients?
Associate Professor Thomas Cox (21:00):
What would be the ideal outcome is that we obviously
confirm safety, and we see efficacy that would match what
we currently are seeing within our animal models, which is
that you would effectively get a reduction in that primary tumour,
that antifibrotic is reducing the level of fibrosis. And, in
(21:20):
the first instance, this would obviously extend the lifetime survival
of patients. But it opens up a really interesting possibility,
which is, that there are often patients which the tumour
has either got too big or has potentially spread locally,
meaning that they're not eligible for surgery. And and currently,
(21:42):
surgery is is really one of the the major and
best options for pancreatic cancer patients. An absolutely fantastic outcome
would be that, as we give our anti-fibrotic in combination
with the chemotherapy, that we see a reduction in that
tumour size, that the tumour does begin to shrink. And
that may potentially make patients eligible for surgery. So, rather
(22:05):
than just having chemotherapy and not being eligible for surgery,
which has a particularly poor survival, being able to shrink
a tumour enough that a surgeon could then get in
and do what they do best, which is to remove
that tumour. I think that's going to be where you'd
start to see some really big increases in overall survival. Because,
(22:27):
once you've removed that tumour, then it's gone. Often very
difficult to do that with chemotherapy alone. So, that would
be our perfect scenario.
Dr Viviane Richter (22:36):
When might we see the results for this clinical trial?
Associate Professor Thomas Cox (22:39):
The clinical trials, once they've kicked off, would still take
a a reasonable amount of time. Even early results probably
wouldn't be until the, you know, a year after you've started.
Some of it comes down to patient recruitment. One of
the key things we want to be doing is to
be selecting the right patients for that potential clinical trial.
(23:02):
One of the things that we can do is, and
we are doing, is attempting to find biomarkers that would indicate, well,
this patient is most likely to respond to the new
combination therapy. It does two things. One is it ensures
we are treating the biology of that tumour correctly. And
so we're not just giving a drug to a patient
(23:23):
that we don't think would respond. But it also spares
ineffective therapies, and so patients don't have to essentially go
through a treatment regime, which wouldn't work. So.
Dr Viviane Richter (23:33):
What patients might benefit most from this new treatment approach?
Associate Professor Thomas Cox (23:37):
Effectively, any solid tumour patient in which we know that
those tumours are accompanied by high levels of fibrosis. So
pancreatic cancer? Definitely. But there are other tumours that tend
to be quite fibrotic. We could think about head and
neck cancer, for example. So, there may well be other
(23:59):
cancers that either present with high levels of fibrosis, so
at the time of diagnosis they may already be quite fibrotic,
but also, as we mentioned earlier in the discussion, sometimes
your therapies can trigger more of that fibrosis to be
laid down, and not all cancers do that. But but
some do. And of course, that would also be another
(24:20):
group where we might be keen to look at with
the combination with an anti-fibrotic and another therapy. Could be chemotherapy, radiotherapy.
Would that also again improve the response to those particular therapies?
Dr Viviane Richter (24:35):
Tom, you've been at Garvan for nearly eight years. Why
is Garvan the right place to do this kind of research?
Associate Professor Thomas Cox (24:43):
Garvan is this incredible mix of ridiculously smart scientists, clinicians,
because obviously the Garvan is situated within the St Vincent's
Hospital precinct. We have the Kinghorn Cancer Centre, which is
actually where my my lab is based, which is a
partnership between Garvan and and St Vincent's. And what that
(25:04):
means is we not only get to interact with scientists
from cancer, biology, immunology, genomics, we get to interact and
embed clinicians within our research who are two floors down
within the patient treatment part. So, they'll be seeing patients
on a regular basis but then discussing the science with us.
(25:28):
It often brings it home because the building we work
in is also a cancer treatment centre. And so we
see the patients and you see them coming in for
their treatments. Uh, and I think that's really important, and
we engage a lot with our consumers. And by consumers,
I'm talking about consumer advocates, individuals who have lived experience
(25:49):
of cancer, either personally or through close friends and families,
and who want to get back involved in the research,
want to bring their perspectives. And Garvan is very good
at this. We have a number of consumers across different
cancer types that give us their input. They're the ones who,
I guess, keep us grounded and help us put what
we do in perspective. And all of this together I think,
(26:12):
you know, including the industry links we we discussed, create
this super team that can tackle some of the really
difficult problems, such as as pancreatic cancer.
Dr Viviane Richter (26:23):
What are these patient advocates telling you about this research?
How do they feel about what you're doing?
Associate Professor Thomas Cox (26:29):
So, they're really excited as well. In pancreatic cancer, there's
not been a lot of movement in terms of improvements
in survival. There have been a number of new therapies
coming through, but for this one it's just a different
way of of tackling it. And I think that's where
the excitement is beginning to grow is that, if this
(26:50):
is going to to work, this could have a huge impact.
And of course, if you're able to double that survival
from currently around about 9% to 20% that would be
a phenomenal, uh, achievement.
Dr Viviane Richter (27:06):
Tom, what drives you for this work day to day?
Associate Professor Thomas Cox (27:09):
So, I've always been a really curious person, and I
had this very unique opportunity at high school to visit
a local laboratory at the University of East Anglia in
Norfolk and to spend the summer in a research lab.
And that really opened my eyes to biomedical research and
(27:34):
academic research. And I absolutely loved that summer. It's something
I will always remember, and it really shaped what I
thought I wanted to do. And so, obviously after that
became undergraduate in biology and then the PhD in cancer biology.
And I was very lucky during my PhD. I had
(27:54):
both an academic supervisor and a clinical supervisor, and he
was very keen to ensure that there was clinical engagement
at a very early sort of stage in the career.
I would go into surgery with them to collect samples
and really began to see what happens to cancer patients
(28:17):
as those tumours grow, see this firsthand, and to take
valuable samples and then use those back in the lab
in my research. And so that really, I think made
the first connection about this isn't just research for research's sake.
There is actually a person at the end of this
that we're trying to do something. Are we trying to
(28:39):
either better treat their tumours? And to me, if what
we can do in the lab can lead to the
improvement in just a single patient's outcome, then I will
be incredibly happy with that.
Dr Viviane Richter (28:53):
Tom, before we let you get back to your research,
it's time to run through the fast five. What was
your first job?
Associate Professor Thomas Cox (29:01):
First job was a PC repair technician at a UK
chain of stores called PC World.
Dr Viviane Richter (29:09):
Do you have a favourite movie?
Associate Professor Thomas Cox (29:10):
Favourite movie. Top Gun. It was something which I watched
many times growing up, and I have an absolute love
for flying to the extent that, for a while, I
actually had my own private gliders. Licence to fly unpowered gliders.
Dr Viviane Richter (29:24):
Do you have a favourite quote or life motto that
really resonates with you?
Associate Professor Thomas Cox (29:28):
Yes. "If you put your mind to it, then anything
is possible," which I first heard in the Back To The
Future movie by Marty McFly. But I actually believe it
comes from a bit earlier than that. I think it
was Benjamin Franklin.
Dr Viviane Richter (29:41):
What's the current book you're reading?
Associate Professor Thomas Cox (29:43):
I've actually got two on the go at the moment.
The first one is called Thinking Fast and Thinking Slow
by the Nobel laureate, Daniel Kahneman, and it sort of
explores how we make decisions. And the second one is is,
I'm actually rereading the trilogy of five books by Douglas Adams,
The Hitchhiker's Guide to the Galaxy. So I'm at book
(30:06):
three at the moment, which is Life, the Universe and Everything.
Dr Viviane Richter (30:09):
Something that's on your bucket list?
Associate Professor Thomas Cox (30:10):
To visit the Galapagos Islands, mainly to go, essentially, to
look at where Charles Darwin initially formed some of the
work behind the Origin of Species. But also because it's
an amazing place to go scuba diving.
Dr Viviane Richter (30:26):
Associate Professor Thomas Cox, thank you so much for joining
us on Medical Minds.
Associate Professor Thomas Cox (30:31):
Thanks, Viv. It was an absolute pleasure.
Dr Viviane Richter (30:34):
If you'd like to know more about Tom's research or
donate to 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
(30:56):
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.
The human body has an incredible capacity to heal itself,
whether it's a paper cut, a broken bone or your
lungs recovering after a chest infection. But not all types
of healing are good for us. Some cancers have hijacked
the healing process to protect themselves from treatments. In today's episode,
(00:21):
we speak to a researcher who will explain how cancers
do this and how his research is paving the way
for better outcomes for patients. 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 Thomas Cox, head
(00:42):
of the Matrix and Metastasis Lab at Garvan. Welcome, Tom.
Associate Professor Thomas Cox (00:46):
Thanks, Viv. Great to be here.
Dr Viviane Richter (00:48):
Tom, where did this idea come from that cancers and
wound healing are linked?
Associate Professor Thomas Cox (00:54):
So, I think a lot of the early work studying
cancer was by pathologists. So, similar to what they do today.
Looking at the tumours under the microscope and trying to
piece together how they're different and why they might be different.
Some of this goes back really to the 1800s where
the pathologists could see that a cancer wasn't just made
(01:18):
up of cancer cells. There was a structure, you know,
around it that was holding those cells into place. And
that structure is very much the same as what we
see in our normal tissues and normal organs. If we
think about the heart tissue or we think about muscle tissue,
we have heart cells but they're held together by a
glue or a scaffold that gives them the shape of
the heart. And so what pathologists had noticed was actually
(01:42):
that this scaffold, this matrix, as we call it, was changing.
It appeared very different, and it was resembling some of
the properties that they could see in wound healing and
in scarring, for example. And so that really kicked off
this idea that you have both a sort of cellular component,
the the tumour cells, but also this extracellular sort of
(02:05):
outside of the cell, and they work together. And then
I guess, a few years down the line, this this
concept started to be refined, the idea that well, when
we think about normal wound healing, so if you or
I cut ourselves or injure ourselves in some way, the
body switches on these incredibly powerful programmes that have to repair.
(02:26):
They have to restore the normal tissue. And what happens
in cancer was that the cancer cells are sort of
activating those similar wound healing processes. And what this results
in really is this sort of idea of a a
healing or wound healing in and around the tumour. But
if we think about normal situations, we think about what
happens when you cut yourself or you break a leg.
(02:48):
That event has finished, and so the body heals. Normally,
it restores that tissue back to its normal status. But
in a cancer, the tumour is still there. And so
what we get is this sort of continual insult to
that tissue. So the the programme is switched on, but
it's never switched off. And this is something that we
(03:09):
do see in other diseases as well. We think about,
for example, lung fibrosis. Or we could think about liver
fibrosis where there's an insult. For example, it could be
smoking or drinking. If you continue to do that, then
this tissue has to continually repair. And what that leads
to is a tissue fibrosis. So, it's exactly the same
(03:30):
as what's happening in cancer is, this body's repair mechanism
is inadvertently essentially feeding into the progression of the tumour.
Dr Viviane Richter (03:40):
What does fibrosis look like? How can we visualise fibrosis?
Associate Professor Thomas Cox (03:45):
So, our understanding of fibrosis is essentially that tissue repair
process that has gone wrong or is not completing its
its programme as it should. The easiest way for you
and I to to think about it, or even to
see that would be scarring. So if we cut ourselves,
(04:06):
if we leave it alone, it would hopefully heal without
a scar. But of course, in some cases it doesn't.
Children are great. They keep picking at them whilst they heal.
And it's that repeated sort of injury. And what you
then get is this scar tissue, and it's it's made
up of this large amount of extracellular matrix, and we
see that we see this sort of white line. And
(04:29):
so that's what we get really in in tumours is
this scarring that forms in and around the tumour. And actually,
that's quite important because very early on, one of the
ways that tumours are diagnosed is there's a lump. There's
something there that wasn't there before, and that's a combination
(04:51):
of both tumour cells, which are expanding, obviously tumour cells
sort of uncontrollably divide, but also some of that fibrosis
that is forming this hard lump. And that's that's often
what you can feel as an individual. And obviously the
doctors would be the first sign that they maybe need
further tests.
Dr Viviane Richter (05:08):
So, what do we know about fibrosis now? Are there
some cancers that are more fibrotic than others? Or is
this potentially the key to a breakthrough for all cancers?
Associate Professor Thomas Cox (05:20):
So, what we know now and and I think, have
done over the last sort of four or five decades,
is begun to really start to understand the biology of
this fibrosis. Why is it important? How does it feed
into the progression of a cancer? And, more importantly, how
might that affect treatments that we give patients? Most cancers,
(05:42):
in fact all solid cancers, when we think about a
solid tumour versus a blood tumour which will have a
matrix will have this fibrotic kind of scar tissue, some
are much, much more fibrotic than others. A good example
of that would be pancreatic cancer, for example, and what
we've begun to understand is the context is incredibly important. So,
(06:08):
the tumour cells within that tumour and within the context
of that fibrosis, that fibrosis is having a huge path
now in how fast they divide, whether or not they
move and spread around the body in the process that
we call metastasis, whether they respond to a particular treatment
or not. And so, what we're starting to do is
(06:29):
think about designing therapies that are not just targeting cancer cells.
What we want to do is to target both the
cancer cells and this support network, or this fibrotic mass,
that forms around them. And in doing so, we now
treat the whole tumour rather than just the cancer cells.
And it's not just that it might be telling a
(06:51):
cancer cell to divide more. It also forms a bit
of a physical barrier sometimes. We think about scar tissue,
it's obviously it's a very dense tissue that can have
an effect of stopping some therapies from getting in as well,
and so part of that is about stopping the fibrosis
from forming. But I think we have to be very careful.
We have to do this in a bit of a
(07:12):
nuanced manner. And the reason I say that was because
a few years ago there was this sort of idea
that, well, if this fibrosis is bad, then well, surely if we
if we just get rid of it, then we will
effectively improve the outcomes in cancer. But what they realised
was you can't just get rid of everything. And we
(07:34):
think back to to what I mentioned earlier about how
all of our tissues in our body have these this matrix,
this tissue sort of structure. That actually is very powerful
in the normal situation of telling the cells what to do. So,
the reason our heart tissue just doesn't continue to get
bigger and bigger is because that tissue structure is saying no,
(07:55):
you're at the right size, now we carry out the function. So,
what we want to do is, rather than get rid
of that fibrosis, is look at how do we either
identify the really what we call pro-tumorigenic parts of it,
or effectively normalise it. So, let's say return it back
to what it should be and ultimately try to close
(08:16):
that loop of that repair mechanism. And in doing so,
I think we're going to be much, much more effective
and essentially improve the efficacy of our already approved standard
of care therapies. And so that's really the goal, I think.
Dr Viviane Richter (08:30):
Are there any particular cancers you're focusing on?
Associate Professor Thomas Cox (08:33):
So, we focus primarily in the pancreatic cancer, breast cancer
and lung cancer space. There's a lot of overlap in
some of these mechanisms when we talk about this tumour fibrosis,
whilst even though the tumours themselves are quite different. And
so we have a number of programmes of work which
are essentially trying to understand both those similarities, but also
(08:56):
those differences, and so can we learn from one type
of tumour and apply it to another. But this is
also important because when you think about a lot of cancers,
they spread around the body, uh, and this process of
metastasis that makes it very difficult to treat. And so
if we think about breast cancer, for example, one of
the common sites it spreads to is the lung tissue.
(09:18):
And so, actually, by studying across multiple cancers and looking
at the tissues, whether it's a primary lung cancer or
a metastatic breast cancer that's gone to the lung, we
can also start thinking about how we might treat these
different tumours based on the organ that they are within,
or based on the tissue remodelling programmes that they activate.
Dr Viviane Richter (09:39):
Why is it so critical to target fibrosis in these
cancers in particular? What is the limitation of current treatments?
Associate Professor Thomas Cox (09:49):
If we take pancreatic cancer as an example, this is
a very fibrotic tumour. Sometimes over 50% of the actual
tumour itself might be this scar tissue. And so effectively,
if we only target cancer cells, we may only be
targeting half of that tumour. But as I mentioned before,
(10:09):
one of the things this scar tissue, this matrix, can
do is blunt the efficacy of therapies that we're giving,
be this a chemotherapy, radiotherapy, even the new immunotherapies.
Dr Viviane Richter (10:21):
Like a physical barrier.
Associate Professor Thomas Cox (10:23):
Yes. And what we've started to realise is that as
we give a therapy, and this is some of the
work from my team, one of the things that happens
is you actually cause damage to the tumour, which is
that actually the therapy doing what it should do. But
of course, that damage, that killing of those cancer cells,
(10:43):
then sort of hyperactivates the body's wound healing response because
there's obviously damage that now needs to be effectively repaired.
And so sometimes your therapies do their job at killing
cancer cells. But one of the, I guess, side effects
is to trigger more of that fibrotic tissue to be deposited.
So this may mean that the tumour goes from 50%
(11:05):
to 60% to 70% and this becomes a problem because
that can stop the successive rounds of therapy getting into
the tumour. It may protect those cancer cells from other,
for example, immune cells. If we think about the context
of immune therapy, which is a new therapy that's been
coming out, and so the idea is, if we can
(11:25):
block that fibrosis at the same time as our therapy,
do we then essentially allow our therapy to continue to
carry its job out effectively? So, another problematic aspect of
this tumour fibrosis is when we come to monitoring patient
response to a particular therapy, especially for tumours that may
(11:47):
be deep inside the body, such as within the pancreas.
And this is because, typically, we may use an imaging
modality or approach like a CT. We hear about CT scans and
what they're doing is they're using these to monitor the
size of the tumour as we give a therapy. And
in many tumours we see the shrinking of that tumour.
(12:09):
And so this is an indicator that we're getting a response.
But in some pancreatic cancer patients and other fibrotic tumours,
what we actually see is that fibrosis replaces where those
cancer cells have been killed. And this means that effectively,
the tumour doesn't look like it's actually shrinking, and so
(12:32):
it can make it very difficult to stage a a
tumour and therefore to determine how effective that treatment might be.
And this is where we get that increase going up from,
you know, 60% or above. And it's not until surgery
and the tumour perhaps comes out that you can then
look at it and say, well, actually, it's mostly just fibrosis now.
(12:54):
The cancer cells have been killed, but it can make
it tricky.
Dr Viviane Richter (12:58):
Tell us what you're hoping to achieve through your research.
Associate Professor Thomas Cox (13:01):
One of the key things we're interested in is understanding
how do all of those building blocks of fibrosis come together?
How do they assemble and and how does that you
know scar tissue form within the tumour. So we've got
quite a large programme of work where we're targeting different
elements of that to try and block that. And the
(13:22):
idea behind that is that if we can prevent or
slow down that formation of that fibrotic tissue, that scarring
within the tumour, whilst we're giving our chemotherapy, then we
effectively make chemotherapy better and therefore hopefully improve the response
of that patient and therefore outcome. We've taken a number
(13:44):
of different approaches to doing this. A lot of what
we do partners with industry and biotech and pharma to
try to develop novel approaches. So, chemotherapy has been around
for for decades. It's tried and tested but this, these
anti-stromal therapies that I mentioned, these anti-fibrotics are very new
(14:06):
to the field of cancer. And so, by combining the two,
we're hoping to show that we can improve outcome in patients.
Dr Viviane Richter (14:14):
So, how do these treatments work? Because I would imagine
that you'd want to not turn off all healing, all
wound healing in the body, so you wouldn't want to
prevent all of fibrosis from happening, I would assume. How
do you specifically target this in a cancer?
Associate Professor Thomas Cox (14:31):
So, what we do in our different cancer models is
we look for things that have been activated in tumours.
If you remember back at the beginning of our chat,
when we were talking about how when we cut ourselves,
the body switches on these repair pathways - very powerful programmes
that are designed to repair the body quickly and then
(14:52):
they switch them off. But in cancers they've obviously switched
on and stay on. And so what we do is
look for those that are switched on and that allows
us to target those specifically. That means that, ultimately, if
a patient's on an anti-fibrotic therapy whilst they have the
tumour in their chemotherapy, then we'll be effectively targeting just that.
(15:13):
Of course, one of the things we will need to
do in the future is to ensure that, if you
were to cut yourself at the same time, that there
weren't going to be adverse effects. But that's obviously something
which we would be doing at that point of clinical translation.
Dr Viviane Richter (15:28):
Where is your research up to now?
Associate Professor Thomas Cox (15:31):
So, at the moment, we are at what we call
the sort of preclinical to clinical translation. So, what that
means is we have been working for a number of
years now with a Sydney-based pharmaceutical called Syntara working through
different generations of small molecule drugs, anti-fibrotics. And so the
(15:52):
idea is that we are showing that they work in
the Petri dish, as you would expect in a lab,
but then transition that into some of our models of
pancreatic cancer, in particular some of our mass models. And
last year we published some research showing that they work
in mass models of pancreatic cancer in combination with a
(16:16):
standard of care chemotherapy. And we see that we get,
and this is a pancreatic cancer model, so we see that
we get a decrease in that fibrosis within those tumours.
This actually leads to a slower growth of those tumours. So,
we've removed this fibrotic signal that's activating cancer cells to grow faster.
(16:37):
We actually saw that it spreads less around the body,
which is very, very important because metastasis is one of
the most complicated and difficult things to treat in patients.
So today, actually, this drug has been tried in what
we call phase one trials, which is to make sure
that the drug still has its same effects within people,
(17:02):
and a trial has been launched in a slightly different
type of cancer called myelofibrosis. This is a fibrotic bone
marrow cancer, if we can call it that. And so
the next step for us is to launch a phase
what we call 1c or 2a trial in pancreatic cancer. Uh,
(17:23):
and the idea of that is to run that at
the Garvan and the Kinghorn Cancer Centre in connection with
our clinical partners across Sydney and Australia. And so the
first thing we've got to do is check whether or
not our new anti-fibrotic drug is going to be safe
to give with chemotherapy. And then, once we're happy that
(17:43):
it's not going to negatively affect the efficacy of chemotherapy,
ask the question of whether or not it improves the
effects of chemotherapy. And so that's really where we're sort
of poised. We are hoping to launch that in 2025.
Dr Viviane Richter (18:01):
Tom, how does it feel to be on the cusp
of launching this clinical trial, which could potentially have a
significant impact for patients?
Associate Professor Thomas Cox (18:10):
So, it's a really exciting time right now. Obviously, a
lot of the work we've been doing is very much
understanding the biology of pancreatic cancer. As we know, it's
got in a terrible survival rate at the moment. Unfortunately,
it's less than 10%. A lot of that is because
there aren't that many effective therapies. Uh, and we really
(18:32):
do need to come up with new ways and new
combinations to, you know, shift that dial to really improve that.
And so this is a a really unique opportunity, I think.
This idea of anti-fibrotics or anti-stromal therapies, as we call them,
is still quite new in the field. There have been
a few trials out there with mixed results because we're
(18:57):
still learning about how that fibrosis scarring feeds into the cancer.
How that might complement, for example, chemotherapy. And at the moment,
from where we're sitting, we've got an incredibly strong signal,
like it's very exciting for us to see this route
to the clinic. And I guess from a personal perspective,
(19:20):
I'm a scientist by training. I I'm one of those people,
I like to understand how things work, but also why
they aren't working. Why are they not doing what they
should be doing and which is obviously what happens in cancer.
And so this idea that we can now take all
that biology, all that understanding that we've generated and the
(19:43):
proof of principle, and transition that through to a potential
therapeutic that may have beneficial effects. I think it would
be hugely rewarding to see a trial kick off that
would pale in comparison if it made a difference to
just a single patient. I would honestly feel that after
(20:04):
about 15 years of, of working in this space almost
on this project, that to see that benefit, even a
single patient would be enormous.
Dr Viviane Richter (20:13):
So, what are you hoping to see from this clinical trial?
Associate Professor Thomas Cox (20:17):
So, the first thing I mentioned we'll be looking into
confirming safety. So, we know that this drug itself is
safe to give to people. But we also need to
make sure that, when given at the same time as chemotherapy,
we don't make any of those classical side effects of chemotherapy.
We don't want to make them worse. And we certainly
don't want to decrease the efficacy of chemotherapy that we
(20:40):
currently have. So, the first is safety. The second is
then efficacy to ensure that it is doing that having
that antifibrotic role and that that is then improving the
response that patients have to chemotherapy.
Dr Viviane Richter (20:54):
In this clinical trial, what would be the best possible
outcome for patients?
Associate Professor Thomas Cox (21:00):
What would be the ideal outcome is that we obviously
confirm safety, and we see efficacy that would match what
we currently are seeing within our animal models, which is
that you would effectively get a reduction in that primary tumour,
that antifibrotic is reducing the level of fibrosis. And, in
(21:20):
the first instance, this would obviously extend the lifetime survival
of patients. But it opens up a really interesting possibility,
which is, that there are often patients which the tumour
has either got too big or has potentially spread locally,
meaning that they're not eligible for surgery. And and currently,
(21:42):
surgery is is really one of the the major and
best options for pancreatic cancer patients. An absolutely fantastic outcome
would be that, as we give our anti-fibrotic in combination
with the chemotherapy, that we see a reduction in that
tumour size, that the tumour does begin to shrink. And
that may potentially make patients eligible for surgery. So, rather
(22:05):
than just having chemotherapy and not being eligible for surgery,
which has a particularly poor survival, being able to shrink
a tumour enough that a surgeon could then get in
and do what they do best, which is to remove
that tumour. I think that's going to be where you'd
start to see some really big increases in overall survival. Because,
(22:27):
once you've removed that tumour, then it's gone. Often very
difficult to do that with chemotherapy alone. So, that would
be our perfect scenario.
Dr Viviane Richter (22:36):
When might we see the results for this clinical trial?
Associate Professor Thomas Cox (22:39):
The clinical trials, once they've kicked off, would still take
a a reasonable amount of time. Even early results probably
wouldn't be until the, you know, a year after you've started.
Some of it comes down to patient recruitment. One of
the key things we want to be doing is to
be selecting the right patients for that potential clinical trial.
(23:02):
One of the things that we can do is, and
we are doing, is attempting to find biomarkers that would indicate, well,
this patient is most likely to respond to the new
combination therapy. It does two things. One is it ensures
we are treating the biology of that tumour correctly. And
so we're not just giving a drug to a patient
(23:23):
that we don't think would respond. But it also spares
ineffective therapies, and so patients don't have to essentially go
through a treatment regime, which wouldn't work. So.
Dr Viviane Richter (23:33):
What patients might benefit most from this new treatment approach?
Associate Professor Thomas Cox (23:37):
Effectively, any solid tumour patient in which we know that
those tumours are accompanied by high levels of fibrosis. So
pancreatic cancer? Definitely. But there are other tumours that tend
to be quite fibrotic. We could think about head and
neck cancer, for example. So, there may well be other
(23:59):
cancers that either present with high levels of fibrosis, so
at the time of diagnosis they may already be quite fibrotic,
but also, as we mentioned earlier in the discussion, sometimes
your therapies can trigger more of that fibrosis to be
laid down, and not all cancers do that. But but
some do. And of course, that would also be another
(24:20):
group where we might be keen to look at with
the combination with an anti-fibrotic and another therapy. Could be chemotherapy, radiotherapy.
Would that also again improve the response to those particular therapies?
Dr Viviane Richter (24:35):
Tom, you've been at Garvan for nearly eight years. Why
is Garvan the right place to do this kind of research?
Associate Professor Thomas Cox (24:43):
Garvan is this incredible mix of ridiculously smart scientists, clinicians,
because obviously the Garvan is situated within the St Vincent's
Hospital precinct. We have the Kinghorn Cancer Centre, which is
actually where my my lab is based, which is a
partnership between Garvan and and St Vincent's. And what that
(25:04):
means is we not only get to interact with scientists
from cancer, biology, immunology, genomics, we get to interact and
embed clinicians within our research who are two floors down
within the patient treatment part. So, they'll be seeing patients
on a regular basis but then discussing the science with us.
(25:28):
It often brings it home because the building we work
in is also a cancer treatment centre. And so we
see the patients and you see them coming in for
their treatments. Uh, and I think that's really important, and
we engage a lot with our consumers. And by consumers,
I'm talking about consumer advocates, individuals who have lived experience
(25:49):
of cancer, either personally or through close friends and families,
and who want to get back involved in the research,
want to bring their perspectives. And Garvan is very good
at this. We have a number of consumers across different
cancer types that give us their input. They're the ones who,
I guess, keep us grounded and help us put what
we do in perspective. And all of this together I think,
(26:12):
you know, including the industry links we we discussed, create
this super team that can tackle some of the really
difficult problems, such as as pancreatic cancer.
Dr Viviane Richter (26:23):
What are these patient advocates telling you about this research?
How do they feel about what you're doing?
Associate Professor Thomas Cox (26:29):
So, they're really excited as well. In pancreatic cancer, there's
not been a lot of movement in terms of improvements
in survival. There have been a number of new therapies
coming through, but for this one it's just a different
way of of tackling it. And I think that's where
the excitement is beginning to grow is that, if this
(26:50):
is going to to work, this could have a huge impact.
And of course, if you're able to double that survival
from currently around about 9% to 20% that would be
a phenomenal, uh, achievement.
Dr Viviane Richter (27:06):
Tom, what drives you for this work day to day?
Associate Professor Thomas Cox (27:09):
So, I've always been a really curious person, and I
had this very unique opportunity at high school to visit
a local laboratory at the University of East Anglia in
Norfolk and to spend the summer in a research lab.
And that really opened my eyes to biomedical research and
(27:34):
academic research. And I absolutely loved that summer. It's something
I will always remember, and it really shaped what I
thought I wanted to do. And so, obviously after that
became undergraduate in biology and then the PhD in cancer biology.
And I was very lucky during my PhD. I had
(27:54):
both an academic supervisor and a clinical supervisor, and he
was very keen to ensure that there was clinical engagement
at a very early sort of stage in the career.
I would go into surgery with them to collect samples
and really began to see what happens to cancer patients
(28:17):
as those tumours grow, see this firsthand, and to take
valuable samples and then use those back in the lab
in my research. And so that really, I think made
the first connection about this isn't just research for research's sake.
There is actually a person at the end of this
that we're trying to do something. Are we trying to
(28:39):
either better treat their tumours? And to me, if what
we can do in the lab can lead to the
improvement in just a single patient's outcome, then I will
be incredibly happy with that.
Dr Viviane Richter (28:53):
Tom, before we let you get back to your research,
it's time to run through the fast five. What was
your first job?
Associate Professor Thomas Cox (29:01):
First job was a PC repair technician at a UK
chain of stores called PC World.
Dr Viviane Richter (29:09):
Do you have a favourite movie?
Associate Professor Thomas Cox (29:10):
Favourite movie. Top Gun. It was something which I watched
many times growing up, and I have an absolute love
for flying to the extent that, for a while, I
actually had my own private gliders. Licence to fly unpowered gliders.
Dr Viviane Richter (29:24):
Do you have a favourite quote or life motto that
really resonates with you?
Associate Professor Thomas Cox (29:28):
Yes. "If you put your mind to it, then anything
is possible," which I first heard in the Back To The
Future movie by Marty McFly. But I actually believe it
comes from a bit earlier than that. I think it
was Benjamin Franklin.
Dr Viviane Richter (29:41):
What's the current book you're reading?
Associate Professor Thomas Cox (29:43):
I've actually got two on the go at the moment.
The first one is called Thinking Fast and Thinking Slow
by the Nobel laureate, Daniel Kahneman, and it sort of
explores how we make decisions. And the second one is is,
I'm actually rereading the trilogy of five books by Douglas Adams,
The Hitchhiker's Guide to the Galaxy. So I'm at book
(30:06):
three at the moment, which is Life, the Universe and Everything.
Dr Viviane Richter (30:09):
Something that's on your bucket list?
Associate Professor Thomas Cox (30:10):
To visit the Galapagos Islands, mainly to go, essentially, to
look at where Charles Darwin initially formed some of the
work behind the Origin of Species. But also because it's
an amazing place to go scuba diving.
Dr Viviane Richter (30:26):
Associate Professor Thomas Cox, thank you so much for joining
us on Medical Minds.
Associate Professor Thomas Cox (30:31):
Thanks, Viv. It was an absolute pleasure.
Dr Viviane Richter (30:34):
If you'd like to know more about Tom's research or
donate to 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
(30:56):
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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Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.
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