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Doug Yee
Cancer Center
PHOTO COURTESY OF UM CANCER CENTER
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The American
Cancer Society created quite a stir when it announced earlier this
year that the actual number of cancer deaths had decreased for the
first time since 1930. While this drop is encouraging, the sheer
numbers associated with cancer remain staggering. The American Cancer
Society predicts that in 2006 almost one-and-a-half million Americans
will be diagnosed with cancer and over one-half million Americans
will die of cancer.
With over 200,000 new cases diagnosed each year in the United States,
breast cancer is second only to skin cancer as the most common cancer
in women, and will affect one in seven women at some point in their
lifetime. At the University of Minnesota, physician-scientist Doug
Yee is waging the battle against breast cancer. Yee, the Tickle
Family Chair in Breast Cancer Research and director of the University's
Breast Cancer Research Program, is actively researching new methods
of both detecting breast cancer and treating the disease. Yee's
work may lead to the development of the next generation of tools
to improve early detection of breast cancer and to care for breast
cancer patients.
Getting high-tech for breast cancer
detection
For women over 40, the standard clinical practice for breast cancer
screening consists of an annual mammogram and clinical breast exam.
Mammography is a small-dose X-ray imaging of the breast used to
look for abnormalities that can then be further evaluated to rule
out or diagnose cancer. A definitive diagnosis of cancer is typically
made by performing a biopsy and examining tissue for the presence
of malignant cells. Yee is studying alternatives to the mammography/biopsy
approach through a collaboration with Michael Garwood of the University's
Center for Magnetic Resonance Research. Garwood and Yee are using
magnetic resonance imaging (MRI) and magnetic resonance spectroscopy
(MRS) for breast cancer screening and diagnosis, respectively.
Magnetic resonance techniques use magnet fields, not X-rays, to
produce images. In Garwood and Yee's work, MRI is first used to
find an abnormality in the breast, then MRS is used to measure molecules
(specifically, choline-containing compounds) known to accumulate
in cancer cells. Different breast tissue types, including both cancers
and non-cancerous masses such as cysts and fibroadenomas, produce
different MRS results (in the forms of peaks on a graph) that allow
the imaged tissue to be characterized as benign or malignant. In
a recently published study, Garwood, Yee, and colleagues found that
the addition of MRS analysis to the diagnostic panel used to evaluate
breast lesions improved the sensitivity and accuracy of radiologists'
abilities to distinguish malignant from non-malignant lesions.
MRI and MRS techniques offer a number of advantages. Unlike biopsy,
MRS is a non-invasive procedure, and use of MRI and MRS may eventually
reduce the number of unnecessary biopsies performed. According to
Yee, MRI may also be a better technology for younger women where
mammography is not quite as accurate. MRI is already becoming a
more common practice for screening women with higher risk, such
as younger women with a genetic predisposition to breast cancer.
However, MRI screening is more expensive than mammography and can
miss some abnormalities that mammography can detect. For this reason,
MRI "is not a replacement imaging technology, but it is complementary
[to mammography]," notes Yee. The MRS diagnostic technology
"is not yet being used clinically, [but] we are very interested
in adapting our research to the more commonly used clinical machines,"
says Yee. MRS techniques may also eventually be used in treatment
protocols to monitor tumor response to cancer therapies.
Studying breast cancer cell signaling
In Yee's laboratory, scientific studies focus on learning more about
the growth factor molecules that send signals to breast cancer cells
to tell them to grow or to spread to other parts of the body. Knowing
more about the signaling molecules and pathways would allow scientists
to develop therapeutics that could interrupt these processes, slowing
breast tumor growth or spread. Therapeutics could be designed to
act in a number of ways, including lowering the levels of signaling
molecules in the circulation, neutralizing signaling molecules or
their activities, or disrupting the binding of signaling molecules
to their targets. This anti-growth factor therapy approach has already
been successfully used to develop two widely prescribed breast cancer
drugs, trastuzumab and tamoxifen.
Yee's particular interests lie in the signaling pathway in which
peptides in a family called the insulin-like
growth factors (IGFs) are the key signal molecules.
He is examining how the actions of IGFs contribute to breast cancer
malignancy, with the ultimate goal of developing anti-IGF strategies
that could be used clinically. Yee has examined how IGFs bind to
their receptors on breast cancer cells. He has demonstrated that
IGF binding to and activation of the type I IGF receptor enhances
cell motility (which would be required for cancer cells to spread
throughout the body) through effects on multiple signaling systems
known to be involved in cell migration. In addition, Yee has also
found that an antibody targeted against the type I IGF receptor
reduces the expression of both the type I IGF receptor and the insulin
receptor on breast cancer cells, making the cells unresponsive to
IGF-I.
Collectively, these studies provide strong support that interfering
with the type I IGF receptor's function or interrupting the cellular
events that occur after IGF binds to and activates the type I IGF
receptor appear to be potential strategies for novel cancer therapies.
Successfully targeting the type I IGF receptor therapeutically,
while promising as an approach, requires overcoming some challenges.
For example, unlike the estrogen receptor, the type I IGF receptor
functions in a variety of cell systems within the body, meaning
any potential therapy would require a mechanism to target it to
the breast cells so as to avoid negative effects on other cellular
systems. However, this issue is not unique to therapeutics targeting
the IGF receptor system.
Customizing breast cancer treatment
With the new technical advances in breast cancer diagnosis,
treatment, and care, the movement in the field of breast cancer
medicine is to no longer treat all patients the same way, but rather
to tailor treatment to the individual patient's tumor. For instance,
the availability of genetic tests allow the likelihood of recurrence
in an individual patient to be assessed, and treatment decisions
made based on that patient's, not an entire population's, risk.
According to Yee, understanding the basic biology of cancer will
lead to the development of better treatment options, and the older
strategy of giving non-specific chemotherapy will be rapidly replaced
by therapies that specifically attack the characteristics of a particular
tumor. Yee's work with the cell signaling pathways involved with
breast cancer growth and metastasis is just one example of this
trend, and may someday provide new therapeutic options for breast
cancer patients.
For more information:
U of M Cancer Center: www.cancer.umn.edu/index.html
U of M Center for Magnetic Resonance Research: www.cmrr.umn.edu/index.shtml
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