George
Coukos, MD, PhD, is conducting cutting-edge
research in the area of early detection
of ovarian cancer, with a focus on tumor
vasculature. Tumor blood vessels are
quite distinct from blood vessels of
normal organs. They are overgrown and
irregular. Dr Coukos
hypothesized that tumor vasculature expresses
unique molecular markers that are ideal
targets for diagnosis as well as therapy.
Dr. Couko’s lab recently discovered
the unique molecular make-up of vascular
cells in ovarian cancer. Using cutting-edge
molecular techniques developed by the
lab, numerous molecules expressed uniquely
by the vasculature of tumors including
ovarian cancer were identified. Because
these molecules are bound to the surface
of tumor blood vessels, they can be used
to visualize tumors in the body using
molecular imaging or even to attack tumors
with smartly designed killer bullets
(targeted therapy). In addition, some
of these molecules may be shed into the
blood stream. These can be detected using
a blood test. This discovery generates
unique opportunities for the development
of early detection tools using serum
biomarkers or molecular imaging as well
as targeted therapy.
Presently, Dr Coukos’ research laboratory is collaborating with other Penn scientists and investigators around the US to develop and validate antibodies against these new tumor vascular markers. Detection of vascular molecules with specific antibodies allows for the visualization of tumors. These antibodies could also be injected directly intravenously to patients to detect tumor vasculature using molecular imaging such as molecular ultrasound or PET scan.
These molecular imaging techniques are
not available presently but the required
underlying technology has been developed
by Penn investigators and can be translated
to the detection of ovarian cancer through
new collaborations that the Penn Ovarian Cancer Research Center aims to establish. Furthermore, markers secreted
into the blood stream could lead to the
creation of antibody-based diagnostic
blood tests. Clearly,
this project holds enormous potential
for advancing the ability to detect ovarian
and other reproductive cancers.
In collaboration with Dr. Coukous, additional
investigators at Penn are working to
develop blood tests for early detection
of ovarian cancer. David
Speicher, PhD, at the Wistar
Institute, an international leader
in tumor proteomics, is using cutting
edge proteomics discovery approaches
to identify proteins in blood that might
herald ovarian cancer. Additional collaborations have been developed
at a national and international level
with groups involved in ovarian cancer
detection.
Recent Advances at Penn in Ovarian
Cancer Prevention
Penn investigators have made important contributions towards understanding the behavior of familial ovarian cancer and identifying optimal ways to manage patients with hereditary mutation of BRCA1 and BRCA2. Steven Rubin and colleagues discovered that patients with hereditary ovarian cancer have better prognosis than patients with nonhereditary tumors. In addition, Tim Rebbeck, PhD, of Penn's Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, and Susan Domchek, MD, who directs the Cancer Risk Evaluation Program, have shown the effects of prophylactic surgery and hormonal therapy, and have conducted ground breaking research to optimize the management of patients with hereditary mutation of BRCA1 and BRCA2..
Penn investigators are working to develop vaccines for the prevention of ovarian cancer. The first ovarian cancer prevention vaccine using dendritic cells loaded with Her-2 and hTERT has been recently initiated at Penn. In this trial, led by Christina Chu, MD, a Penn gynecologic oncologist, we are testing the hypothesis that vaccination against these two tumor proteins could prevent tumor recurrence in patients with HLA-A2 blood type and stage III or IV ovarian cancer who have experienced a complete response to front line chemotherapy.
If safety and efficacy of this vaccine is confirmed, this approach may be applied to earlier stages of the disease, vaccinating patients with stage I or II disease who are at risk of tumor recurrence. Eventually, similar approaches may be used to prevent ovarian cancer in healthy women with family history of hereditary ovarian cancer due to BRCA1 and BRCA2 mutations.
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