Recent advances at the Center for Research on Early Detection and Cure of Ovarian Cancer
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 for clinical testing 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 Center for Research on Early Detection and Cure of Ovarian Cancer 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.
Additional investigators in the Center 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.
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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