| Breast
Preclinical Research Program
Lucio Miele, MD, PhD, professor, Loyola University
Chicago Stritch School of Medicine (Stritch),
Department of Pathology, directs the Breast Preclinical
Research Program, which is focused on basic science
research of breast cancer. The program includes
several research teams that are exploring novel
breast cancer medications, therapeutic targets,
diagnostic biomarkers and sophisticated investigations
of the molecular basis for rational and targeted
therapies.
Notch
genes
Dr. Miele’s laboratory is nationally recognized
for its study of “Notch” genes in
breast cancer. This research guides the development
of novel medications that already are in clinical
trials. The research also aids the discovery of
additional ways to target these genes to prevent
or treat resistance to antiestrogens and to the
drug trastuzumab. It appears that these Notch
genes represent an emergency escape mechanism
that is triggered by treatment with diverse breast
cancer drugs and then helps cancer cells survive.
Promising therapeutic combinations developed in
Dr. Miele’s laboratory eventually will be
offered to patients in the clinical research setting
by the Breast Clinical
Research Program team. Dr. Miele’s group
is collaborating with Kathy Albain, MD, Katharine
Yao, MD, Prabha Rajan, MD, and other members of
the program to develop novel genetic tests based
on his group’s research that can better
define the potential for recovery of breast cancer
patients. The preclinical research group also
participates in clinical
trials initiated by clinical research program
physicians by evaluating novel molecular markers
in patient biopsies or surgical specimens.
Notch
and breast cancer cells
Approximately
80 percent of breast cancers are defined as "estrogen
receptor positive" or estrogen-positive tumors.
Patients with estrogen-positive tumors are treated
with drugs that block the estrogen receptor or
block the body's production of estrogen. However,
some cancers do not respond well to this treatment,
and some become resistant and the cancer recurs
after initially responding. This is a major clinical
problem.
Research
by Paola Rizzo, PhD, assistant professor, Stritch,
Department of Pathology, has determined that estrogens
block the activity of "Notch receptors"
in breast cancer cells. Conversely, when breast
cancer cells are treated with drugs such as tamoxifen
that block estrogen inhibitors, the cancer cells
respond by reactivating the Notch receptor. These
help breast cancer cells survive and could make
the cells more resistant to further treatment.
Based
on these studies by Dr. Rizzo, Dr. Miele's team
has determined that a combination of anti-estrogen
medication plus a new drug that blocks Notch receptors
can make estrogen receptor positive tumors shrink
and disappear (in studies in mice). A clinical
trial of a similar combination is planned at Loyola
in the near future and may open the way to the
development of new treatment regimens.
Her2/Neu
oncogene and Notch
Approximately
30 percent of breast cancers are very abundant
with the Her2/Neu (or ErbB2) cancer receptor.
These cancers tend to be clinically aggressive
and are often not responsive to drugs that block
estrogen receptors. Currently, treatments for
these cancers include trastuzumab and lapatinib,
a newer drug that blocks the enzymatic activity
of the Her2/Neu protein and other related receptors.
Research
by Clodia Osipo, PhD, assistant professor, Stritch,
Department of Pathology, has determined that treating
the Her2/Neu positive breast cancer cells with
trastuzumab or with a class of drugs similar to
lapatinib leads these cancer sites to respond
by re-activating these Notch receptors, just as
observed for estrogen-blocking drugs. The Notch
receptors help breast cancers survive and possibly
become resistant to trastuzumab or lapatinib.
Studies conducted in cells grown in the laboratory
have shown that when a new drug that blocks Notch
receptors is given along with the drugs trastuzumab
or lapatinib, their effectiveness is greatly increased.
If preclinical research proves effective, planning
for clinical trials will begin.
Breast
cancer stem cells
The preclinical research group that Kimberly
Foreman, PhD, associate professor, Stritch, Department
of Pathology, directs is studying the newly discovered
“breast cancer stem cells,” rare cells
that give rise to breast cancer recurrences and
metastasis (the spread of cancer) and studying
novel ways to eradicate these cells. Stem cells
have the remarkable potential to develop into
many different cell types in the body. Additionally,
Dr. Foreman is investigating normal human adult
stem cells not derived from human embryos, and
the "communication" between breast cancer
cells and blood vessels.
Psychological
stress reduction techniques
Herbert
Mathews, PhD, professor, Stritch, Department of
Microbiology & Immunology, directs a group
that is conducting research on the
effects of psychological stress reduction techniques,
such as the mindfulness awareness program, on
breast cancer patients’ immune systems.
Understanding this aspect of the mind-body connection
will improve our ability to increase patient well-being
and the effects of treatment.
Receptor
function
Adriano Marchese, PhD, assistant professor,
Stritch, Department of Pharmacology & Experimental
Therapeutics, leads a group in his department
that is studying the function of CXCR4, a receptor
that is crucial for metastatic spread of breast
cancer cells through the body. His work may lead
to the discovery of novel agents that prevent
such metastasis, or the spread of cancer.
Bio-informatics
The
preclinical research program also takes advantage
of constant collaboration with Chindo Hicks, PhD,
and Leo Wang-Kit Cheung, PhD, both assistant professors
at Stritch, Department of Preventive Medicine
& Epidemiology. The two are internationally
renowned experts in bio-informatics, the discipline
that uses highly powerful computer algorithms
to study gene expression patterns that can help
predict disease outcome.
To
find out more about our breast cancer clinical
trials, please call (888) LUHS-888.
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