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Originally posted October 13, 1999
ANN ARBOR, Mich. - Just like the smallest
flaw in Achilles' strength led to his downfall, the smallest
proteins produced by cancer cells may someday give doctors
new ways to find tumors earlier than ever, determine quickly
how malignant they are and target them with customized therapies.
Now, a five-year, $10 million effort at the University of
Michigan Comprehensive Cancer Center will take aim at this
potential vulnerability using the latest technology and biomedical
knowledge.
The multidisciplinary research effort is among the first
in the world to go after cancer in this new way. It will systematically
study the proteins that tumors make, the genes that instruct
the cells to make them, and the subtle differences among proteins
made by different types of tumors.
The U-M research will focus at first on colon, lung and
ovarian cancers, which have defied scientists' efforts to
find characteristics that can distinguish deadly forms from
less malignant varieties. Eventually, the approach should
be applicable to other kinds of cancer, notably breast, prostate
and childhood tumors.
The effort will be led by U-M pediatric oncology professor
Samir Hanash, M.D., Ph.D., and funded by two grants from the
National Cancer Institute.
The funding will allow a U-M team and their U.S. and international
partners - including medical, computer, chemistry and information
specialists - to develop specialized rapid-analysis technology
that can look at all the genes and proteins in tumor cells
taken from cancer patients.
The project will build on work in the U-M's Medical School
and Chemistry Department to identify proteins released by
tumors or found on their surfaces. Some of these proteins
are candidates to become biomarkers, early indicators or Achilles'
heels for different types of tumors.
"This cutting-edge technology has the potential to yield
real breakthroughs in cancer research," says Hanash. "We hope
to further understand the molecular character of tumors so
we can detect them while they are small and predict their
behavior, including the likelihood that they'll respond to
various treatments."
Adds U-M Medical School Dean Allen Lichter, "This research
will lead to dramatic new ways to approach cancer. By detecting
the chemical signatures of cancers, we will be able to make
diagnoses much earlier and be able to tell which cancers are
likely to act aggressively and need early treatment. We are
proud to use our research strength to help speed the pace
of discovery in the important research area."
The molecular approach to cancer research has become possible
in recent years due to advances in the study of proteins and
DNA, the development of new computerized technology for medical
research, and the cooperation of hospitals to save and study
tumor tissue from cancer patients.
The wide search for biomarkers is a new concept made possible
only through the increased understanding of how proteins function
in the body, and how genes control the production of those
proteins in both normal and cancerous cells. In turn, the
understanding of human genes has accelerated in recent years
due to the efforts of the federal government's Human Genome
Project to find and sequence every bit of DNA in the human
body.
The U-M protein-gene project will look at tumor genes and
their proteins simultaneously, starting with advanced-stage
colon tumors, a type of ovarian cancer and two kinds of lung
cancer.
The researchers expect to analyze more than 1,000 different
proteins from each kind of tumor, both by finding their distinguishing
physical characteristics and establishing how abundant they
are. Simultaneously, they will use genetic analysis tools
known as DNA microarrays, as well as other DNA analysis technology
and highly sensitive, high-speed software previously developed
by Hanash's group to determine which genes in a tumor cell
are altered, and which have been switched "on", or expressed,
to create proteins.
All of this information about proteins and genes will help
establish a better way to classify tumors and predict which
ones will be most dangerous. That kind of knowledge can help
doctors plan treatment, and allow researchers to develop treatments
that attack specific kinds of tumors.
The biomarker portion of the project, meanwhile, will look
for those tumor proteins - or leftover immune responses to
them - in blood. Past research has shown that the body can
react to new cancer cells as if they were invading organisms,
and that this immune response leaves behind tumor-specific
antibodies that can be detected in the bloodstream long before
a tumor has grown large enough to be found. Or, the blood
might contain proteins that tumor cells have secreted, or
released, as part of their growth.
The U-M researchers will search for these biomarkers and
develop tests for them. Their effort could give doctors a
head start in finding cancer while it can still be treated
effectively, and in determining exactly what kind of cancer
a patient has so that they can plan for treatment.
The research will rely in part on the Michigan-Ohio Community
Clinical Oncology Program, directed by U-M Medical School
professor Dean Brenner, M.D., which develops innovative strategies
for cancer prevention.
With Hanash and Brenner, other U-M researchers on the project
include: · Co-principal investigators David Beer, Ph.D., associate
professor, Medical School; Kathleen Cho, M.D., associate professor,
Medical School; Eric Fearon, M.D., Ph.D., professor, Medical
School; Thomas Giordano, M.D., associate professor, Medical
School; Jeremy Taylor, M.D., professor, School of Public Health
and Medical School.
Co-investigators Vicki Baker, M.D., professor, Medical School;
Laura Beretta, Ph.D., assistant professor, Medical School;
Stephen Gruber, M.D., assistant professor, Medical School
and School of Public Health; Sharon Kardia, Ph.D., assistant
professor, School of Public Health; Rork Kuick, project coordinator,
Medical School; David Lubman, Ph.D., professor, College of
Literature, Science & the Arts.
Co-investigative collaborator Thomas Glover, Ph.D., associate
professor, Medical School.
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