Dr. Christopher Wolfgang, Chief of Surgical Oncology at Johns Hopkins, discusses the Pancreatic Cancer Precision Medicine Center of Excellence (PMCOE) …
>> My name is Chris Wolfgang
and I'm the Chief of Surgical Oncology
at the Johns Hopkins hospital
in Baltimore Maryland.
It is my pleasure to share an update
on the research that
philanthropy is making possible,
in our program, specifically,
the Pancreatic Cancer Precision Med Center
of Excellence at Johns Hopkins.
This center is a
multidisciplinary research group
which consists of medical oncologists,
radiation oncologists,
surgical oncologists
as well as pathologists, basic scientists
and others who are working together
to do basic translational science,
to find better ways of treating
and hopefully curing pancreatic cancer.
The biology of pancreatic
cancer is somewhat unique.
Like most cancers, it has the propensity
for metastatic disease.
However this propensity is much higher
than most of the other types of tumors,
such as for colorectal cancer
and some of the more common
GI cancers that we hear.
Another example is breast cancer,
which has a relatively low propensity
but not zero propensity to metastasize.
The reason that this is important is
that most patients die
of metastatic disease
when they die of cancer.
And so this is the key
to improving therapy.
Now with pancreatic cancer
we've made several observations,
as usually by the time
we diagnose the disease
the vast majority of
patients are systemic.
So they already had metastatic disease
and there's very little chance for a cure.
What that tells us is that we need
better methods of early detection
and a group at Johns Hopkins
is working on early detection
for pancreatic cancer.
Now in those patients who
are the minority of patients
who present with clinically
localized disease,
that is a tumor localized to the pancreas
with no metastatic spread.
Those are the patients who
have a chance to be cured
from surgical resection.
The problem is that
although we are successful
in taking out the tumor and
ridding them of gross disease,
over 80% will relapse
with metastatic disease,
with metastatic cancer
and die of their disease.
What this tells us is that long
before we knew of the tumor,
long before we took the tumor out
that it had become systemic.
This is most likely through
circulating tumor cells.
Circulating tumor cells are
shed from the primary tumor
released into the bloodstream
and circulate throughout the body.
They're important because
they're not metastasizing
of themselves but they are
the seeds of metastasis,
just like when you plant
grass seed in the yard
it grows into grass,
these cells are like the
seeds of metastatic disease,
they can lay dormant for years
or they can activate sooner
and cause metastatic recurrence.
And so we have a novel way of
thinking of pancreas cancer,
we think of two phases, a
solid phase and a liquid phase.
And in those patients who
have localized disease,
surgical resection with sometimes
the adjunctive radiation therapy,
is good therapy for their local disease.
Yet we fail most of the time systemically.
So we've moved from looking
at the primary tumor
which has given us very
much important information
about the biology of the disease
and we know that pancreatic cancer
represents many different diseases,
from understanding the tumor
biology of the primary tumor,
but we've moved from this,
to studying the disease
that we leave behind.
The reason that this is possible now
and wasn't possible previously,
is that we recently were able to identify,
what we call, minimal residual disease.
That disease that we leave
behind after surgery,
in particular, in the blood
but also in the bone marrow
and in small deposits within the liver,
and for the first time are
able to characterize and study
these few cells that remain behind.
This could be as little as 50,000 cells
as opposed to a patient who
still has an untreated cancer
with literally millions
or billions of cells.
Now these cells, what is interesting
is that they're are different
than the primary tumor.
They behave differently,
and that they are able to
propagate and renew the tumor
unlike most of the cells
within the primary tumor
so they have stem cell-like features.
We also know that they're are
much more mesenchymal type
than epithelial type,
and not all of the circulating
tumor cells are the same.
There's only a small subset
that are the aggressive cells
that are capable of establishing a tumor.
What is so exciting about this,
is being able to study
what we leave behind,
for the first time,
gives us the opportunity
to understand how these cells behave.
So what is their strength
and what is their weakness?
How do they evade immune system,
what type of pathways
are they dependent on?
Do they have some weakness,
for a certain type of therapy
that already exists that
we've never employed
because the biology is so different
than the biology we studied before?
And these are all types of questions
we're seeking answers to.
The reason that philanthropy
is so important,
is that in traditional funding
of biomedical research,
typically the applications in the funding
for this type of research requires
a significant amount of
preliminary data and rightly so.
However when you have a
good idea and a hypothesis
but very little preliminary data,
the only way to generate preliminary data
is to do the research.
Philanthropic support allows
us to take a good idea
and to develop it and further explore
if it is something that truly
is important for patients.
And through philanthropy
and our preliminary research
we were able to identify
circulating tumor cells.
We were able to subtype the
different types of cells,
establish that they were
derived from the tumor
and we are able to,
find them, residual areas
of these microscopic cells
within the body and so basically,
we can now hunt them
down and understand them,
We hope that through this research
and the preliminary data
that were now generating,
that we can expand upon this
and this may be the key to
having more cures in the future.
For example, we have patients,
who have had their tumors removed
who look absolutely normal
with no evidence of recurrence
and we are able to isolate,
circulating cancer cells from their blood.
So we know that these cancers are there.
Now if they are to get their cancers back,
we presume that they
come from these cells,
and so for the first time,
we have the possibility of
seeing what these cells are
and having the potential to intervene.
And so I think you can see that
philanthropic support of
research is highly important.
It doesn't take the place of NIH research
and other large foundations,
but certainly, it goes
hand-in-hand with these foundations
because it supports a
different type of initiative.
These sort of, moon-shot projects,
are thinking outside of the box
really have no funding mechanisms,
and in our institution,
philanthropy has really initiated,
many promising projects, many of these,
have actually translated
into starting new fields
as we hope this will do.
And bringing in substantial research
from the money from the
traditional funding agencies.

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