Diane J. Rodi – Principal Investigator

 

Project Members

   
Suneeta Mandava 

 

Diane Yamada  (Collaborator - University of Chicago College of Medicine )

 

 


Ovarian cancer (OVCA) claims the lives of more women in North America each year than all other gynecologic malignancies combined. The high overall mortality from OVCA is primarily due to delays in diagnosis – although 90% of patients with early stage disease can be cured, 70% of patients at diagnosis have Stage III or higher disease, where the 5 year survival rate is only 20%. At present, there is a dearth of clinically useful antigenic markers for early stage disease. The currently used serum marker CA-125-II has limited sensitivity and specificity for detecting small volume, early stage disease, with a positive predictive value of less than 10%.


We propose to use differential screening of phage displayed libraries to identify cell surface markers specific to ovarian cancer.  The identification of an ovarian carcinoma cell-specific surface marker which is expressed early in tumorigenesis would have an immediate and substantial impact not only on diagnosis, but on development of receptor-mediated anti-cancer therapies.  

Ovarian variation. Using in situ hybridization, researchers can study expression of the oncogeneWT1 in ovarian cells

Phage-display derived peptides or antibodies selected for specific affinity to ovarian carcinoma cells can provide the basis for diagnostic tests for ovarian cancer and/or for targetting therapeutics to transformed cells. Analogous applications have been demonstrated for other systems (e.g., Trepel et al, 2002).  For instance, successful organ targeting has been achieved with a chemically-coupled therapeutic construct (peptide-doxorubicin) (Arap  et al, 1998).  Peptide-bearing phage targeted to a cell surface receptor have been used successfully for gene therapy applications (Larocca et al, 1998; Poul et al, 1999) and for the induction of peptide-mediated endothelial cell apoptosis in targeted tissue (Ellerby et al, 1999 ). 

Cells of an ovarian cancer tumor treated with Exherin viewed through a light microscope.  The vessel has ballooned and ruptured, allowing red blood cells (RBCs) to pool and escape into the tumor

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