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Creating a new oral tradition
June 2012
EDIT CONNECT
SHARING OPTIONS:
NEW YORK—Patients with oral cancer may have more targeted,
personalized treatment options available to them
if a new clinical study
successfully identifies genomic markers in tumors that predict if an oral
cancer is likely to metastasize to the neck.
The study, the work of the NYU College of Dentistry and the
Helen Diller Family
Comprehensive Cancer Center at the University of
California-San
Francisco (UCSF), was recently awarded a two-year grant from the
National Cancer Institute (NCI), part of the National Institutes of
Health
(NIH). More funding is needed to advance the trial, but the study's leaders are
confident that they will be able to harness the power of
genomics to yield
groundbreaking results for oral cancer patients, for whom current treatment
options are limited.
Oral cancer, a subtype of head and neck cancer, is any
cancerous tissue growth located in the oral cavity. Oral cancers may
originate
in any of the tissues of the mouth, and most commonly involve the tongue—but
the disease may also occur on the floor of the mouth, cheek
lining, gums, lips
or palate.
"People don't realize that oral cancer is an incredibly
difficult-to-treat cancer," says Dr. Brian L. Schmidt, professor of oral and
maxillofacial surgery at the NYU College of Dentistry, former faculty
member at
UCSF and a leader of the study. "Head and neck and oral cancers have a lot of
DNA mutations, so it is a very tricky cancer when you compare
it to other
cancers. People don't realize they can die from this, but in fact, survival is
very poor, with about half of patients surviving only five
years after
diagnosis. One of the things that drew me to treating patients with oral and
head and neck cancer is that they often have a low quality of
life. They can
have a lot of pain or disfigurement, so this is a group that needs a lot of
attention."
Oral cancer is often fatal if it spreads to the neck and
remains untreated. Nearly all cancers within the oral cavity must be surgically
removed in a neck dissection, which may also be performed to remove lymph nodes
if there is any clinical or radiographic evidence of neck metastasis.
Current
clinical and radiographic examination provides limited information for
diagnosis of early neck metastasis of oral cancer.
"We currently have no reliable methods of detecting whether
a patient already has metastasized disease. The
instruments we have cannot
detect small metastasis," says Schmidt. "When I finished my fellowship in 2002
[in head and neck
cancer at Legacy
Emanuel Hospital and Health Center in Portland, Ore.],
the Human Genome Project was just being completed. I realized there was the potential
that this
could be used to somehow predict which patients might develop
metastasis."
Enter his colleague,
Dr. Donna G. Albertson, a professor at
the UCSF Helen Diller Family Comprehensive Cancer Center. Albertson, one of the
pioneers in the development of
fluorescent in-situ
hybridization (FISH) and its applications in single-copy gene mapping in the
human, is working to develop microarray
technology for measurement of DNA copy
number alterations, and applications of this technology in medical genetics and
studies of genomic alterations
in cancer.
"We had a project to see if we could find genomic copy
number alterations that were
biomarkers for metastasis of oral cancer,"
Albertson says. "If you can use a brush or swab to take a sample of cells from
the cancer, you can isolate
DNA from that material and carry out the assay for
the biomarker. Such a test could be performed during routine office visits
prior to surgery, and one
could have the answer back quickly—in time to plan
surgical treatment. Use of the swab or brush looks very promising."
Grant funding has been used to develop that assay, but there
is more work to be done and other problems to solve—and thus,
more funding to
obtain. Patients who present with no evidence of metastasis in the neck often
undergo a preemptive neck surgery, because untreated
occult metastasis reduces
life expectancy by half.
"Right now, we just throw everything we can
at the patient,
assuming the patient is going to have the worst possible outcome," says
Schmidt. "Many people are receiving neck dissections to
remove the lymph nodes,
but they are not necessarily benefitting from it. These are significant
surgeries. There is morbidity associated with it,
including a high rate of
stroke compared to other surgeries. In addition, patients have a long recovery
time and have to spend extra time in the
hospital and delay going back to work,
so there are significant downsides to performing neck dissections when it comes
to patient productivity and
healthcare time and costs."
In a larger confirmation study, Schmidt and Albertson will
work to
validate genomic markers that will ultimately be used to rule out neck
dissection in oral cancer patients with no clinical evidence of neck metastasis
and who have tumors containing specific genomic profiles.
Schmidt will conduct the clinical
portion of the study
through the NYU Bluestone Center for Clinical Research, which he directs,
recruiting subjects, enrolling patients and collecting
specimens. The samples
will then be sent to Albertson's laboratory at UCSF, where her team will
process and analyze the samples.
Ultimately, Schmidt and Albertson foresee improved care for
oral cancer patients once their newly identified genomic marker is validated.
"It has taken us eight years of research to converge on a
genomic marker that could be used to
tailor treatment for oral cancer
patients," says Schmidt. "We look forward to testing this marker in a clinical
study, and this funding will help up
us to develop the appropriate laboratory
test for such a trial."
Code: E061218 Back |
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