 |
 |
 |
| |
Click here
for video
|
|
David
Krag, MD
|
|
|
 |
|
 |
Dr.
David Krag has been developing new methods
for treating cancer for more than 20 years. He
has been in Vermont since 1991 and was the first
Fellowship trained Surgical Oncologist in the
State of Vermont. In the early 1990’s Dr.
Krag was Founder of the University of Vermont
Breast Center which now a model of multidisciplinary
care of breast cancer patients as well as patihas
been developing new methods for treating cancer
for more than 20 years. When he came to the University
of Vermont in 1991, he was the first Fellow in
Surgical Oncology in the state of Vermont. Dr.
Krag was a founder of the University of Vermont
Breast Center, which is now a model of multidisciplinary
care of breast cancer patients and patients with
other types of cancer. The Breast Center was set
up to provide outstanding care following accepted
principles and importantly to develop entirely
new methods of treatmentents with other types
of cancer. The Breast Center was set up around
a system of providing outstanding care and importantly
as a center for developing entirely new methods
of treating cancer patients.
Dr. Krag can be called a “translational
researcher,” meaning that he brings new
options for cancer care directly from the research
lab to his cancer patients. Research and treatment
are intertwined. Patients who choose to participate
in new treatments have the chance to inform further
research. Dr. Krag’s ability to translate
the complexities of the science for patients is
critical to the wellbeing and decision-making
of patients.
One
of the best examples of Dr. Krag’s research
going from lab bench to bedside has been the development
of a technique resulting in a major improvement
for surgical management of lymph nodes for breast
cancer, malignant melanoma and other types of
cancer. This new technique Involves injection
of a radioactive tracer that guides the surgeon
to the lymph nodes most likely to contain cancer.
The surgeon can then remove only a few lymph nodes
as a first step in treating the cancer. Removing
only a few lymph nodes rather than the usual method
of removing all of the lymph nodes greatly reduces
the side effects of surgical treatment of cancer.
THE
CONVENTIONAL METHOD FOR TREATING BREAST CANCER
Conventional surgical treatment of breast cancer
currently involves removal of both cancer in the
breast and lymph nodes in the armpit. Breast cancer
commonly spreads to these lymph nodes. The standard
surgical approach is to remove all the lymph nodes
whether they have developed cancer or not. The
unfortunate side effects of this surgery include
lymphedema (swelling of the arm and breast), increased
risk of infection, decreased function and mobility
of the arm, and pain. About two-thirds of women
with breast cancer and four-fifths of melanoma
patients do not have cancerous lymph nodes at
the time of the surgery. For them, removal of
the lymph nodes has no therapeutic value.
RADIOACTIVE
TRACER INJECTION
Removing only the lymph nodes affected by
cancer would make patients’ recovery
easier and equally assured. The challenge
was to identify the lymph nodes with cancer
so that only those could be removed surgically.
Dr.
Krag developed a method of injecting a radioactive
tracer into the breast cancer which tags
the lymph nodes receiving lymph drainage
from the cancer. These are the lymph nodes
that are most likely to have cancer in them.
These lymph nodes become slightly radioactive
and are identified at surgery with the use
of a hand held radiation detector. Instead
of removing all of the lymph nodes, only
the few radioactive nodes are removed. This
is usually only 1 or 2 lymph nodes rather
than the average of 15 nodes. If these radioactive
nodes, called sentinel nodes, do not have
cancer, the rest of the nodes will not have
cancer, and no further surgery is necessary.
This technique spares about two thirds of
women with breast cancer from needing to
have all of their armpit lymph nodes removed.
After
developing this methodology, Dr. Krag designed
and implemented studies to validate the
technical aspects of the procedure and a
large clinical trial to compare the effectiveness
with conventional surgery. This effort has
taken more than 10 years, and all three
phases are nearing completion. The last
phase involved teaching the radioactive
tracer methodology to more than 250 surgeons
at 72 centers in North America. The trial,
led by Dr. Krag, has been the largest surgical
trial for breast cancer in the world.
The
trial is demonstrating the safety and therapeutic
value of the radiotracer method of sentinel
node surgery. This procedure is now the
preferred method of managing breast cancer
and has been adopted in more than 35 countries.
The
radiotracer technique for surgical treatment
of lymph nodes illustrates how a focused
group of individuals can have an impact
on the care of cancer patients. Accomplishing
this feat has taken an enormous amount of
effort and significant financial support.
Most of the funding for all three phases
came from the National Cancer Institute.
Private support was essential at the earliest
phase of this research, and Dr. Krag and
his team remain grateful to the donors.
Without their early vision and support,
there would be no radiotracer sentinel node
program. |
The
above pictures courtesy of www.health.yahoo.com
and are viewable in their original context
by clicking
here. |
CUSTOMIZED
CANCER DRUG
Cancer drugs cause serious side effects.
These powerful drugs, designed to stop cancer
cells from growing, are also toxic to normal healthy
cells. The side effects are unpleasant and severe.
When cancer drugs destroy healthy immune cells
that originate in the bone marrow, it leaves the
body essentially defenseless. This can lead to
life threatening infections and other illnesses.
Wouldn’t
it be wonderful if the cancer drugs could be redesigned
so that they stick preferentially in cancer cells
and not accumulate in normal cells. As the cancer
drug circulates throughout the body, the cancer
cells would soak up the cancer drugs because the
drug has been modified to bind specifically to
the cancer cells. This would result in high concentration
of the cancer drug right in the cancer. This would
lead to increased killing of the cancer cells.
Normal noncancer cells of the body would be exposed
to lower concentration of drug and harmful side
effects would be diminished.
The
Krag lab has been working for more than 10 years
to develop a process to make drugs that will preferentially
target and bind to cancer cells. Importantly,
the Krag lab is focused on developing the techniques
to make customized drugs – drugs that would
be designed to bind to any individual cancer patient’s
cancer cells.
This
research begins with the generation of a very
large set of different drugs. Each member of this
set or “library” of drugs has been
modified slightly so that it is different from
every other drug in the library. Each drug in
the library has slightly different properties,
such as shape or size, which would make it tend
to be sticky to different targets. The number
of different drug molecules in this library is
huge and is greater than the number of all the
books in the University of Vermont College of
Medicine Library.
The
next step is to find out which drug molecules
from this huge library stick preferentially to
cancer cells. This very challenging research is
currently the key focus of the Krag lab. Although
the details are complex, the concept is simple:
The cancer drug library is injected into the bloodstream
of the cancer patient just prior to surgery. The
millions of different drug molecules circulate
throughout the bloodstream, and the ones that
stick preferentially to cancer cells accumulate
in the cancer. The cancer is surgically removed
and the molecules that stuck to the cancer are
recovered. The Krag lab has recently performed
this innovative procedure in patients and this
is the first time in the world that this has ever
been performed.
DETECTION OF HIDDEN CANCER CELLS
Fortunately after surgical removal of breast cancer
or malignant melanoma, most patients are cured.
Unfortunately we do not yet have the ability to
identify patients that already have small numbers
of cancer cells spread through the bloodstream
and growing in different parts of the body. Until
a cancer grows big enough to cause a lump or mass
visible on an x-ray or it begins to cause problems,
it cannot be detected.
It appears that one technique to detect cancer
cells earlier than currently possible is with
a blood test designed to identify rare cancer
cells that may be lurking in the blood. The Krag
lab has been working on this problem and has now
developed a technique using microscopic detection.
This method is very sensitive and can detect one
cancer cell in a mixture of more than 1,000,000
normal blood cells. As with development of the
radio-labeled sentinel method, Dr. Krag is moving
this technology from lab bench to bedside. A large
study that will involve many centers in North
America and involve more than 1,600 breast cancer
patients is about to begin. The goal is to determine
in newly diagnosed breast cancer patients whether
this simple test can identify those patients that
have cancer cells remaining in their body following
all their treatments. This research should take
us one step closer to a cure for breast cancer.
|
