Abstract
Ovarian cancer is a very aggressive disease that is mostly asymptomatic at early onset. Approximately 85% of patients are diagnosed at late-stage disease, which greatly compromises full recovery. Standard detection methods include measurement of the ovarian cancer biomarker CA-125. However, CA-125 is associated with false positive diagnosis and is largely limited to late-stage disease. As a result, there is a great need to discover new biomarkers and develop novel detection and imaging methods for ovarian cancer. Patients with ovarian cancer often respond to initial chemotherapy but most will succumb to recurrent disease. Such poor prognosis is associated with a drug resistant subpopulation of cancer cells with stem-like properties known as cancer stem cells (CSC). Traditional chemotherapy fails to target CSC, and it is widely accepted that this process leads to the recurrence of more aggressive tumors. Therefore, it is essential to discover new ovarian CSC biomarkers and develop therapies that specifically target this subpopulation. Bacteriophage (phage) display technology allows identification of high affinity peptides by screening of peptide libraries against cellular targets. The large amount of unique peptides in a library facilitates high throughput selections both in vivo and in vitro. Here we discuss how phage display can be utilized to discover novel peptides with high binding affinity for normal ovarian cancer cells and ovarian CSC. Such peptides may be radiolabeled and employed in SPECT and PET imaging as well as in therapeutic settings. Further, both phage and phage display derived peptides can be employed in identification of targeted antigens and novel ovarian cancer biomarkers using mass spectrometry analysis. Such biomarkers may be utilized in diagnosis and in identification and selection of ovarian cancer subpopulations.
Highlights
Ovarian cancer is the fifth leading cause of cancer deaths in women and is the most lethal of the gynecological malignancies [1,2]
Survival times as low as 24 months post diagnosis [1,6,7,8,26]. Such poor prognosis seems to result from chemotherapy treatment that targets only the bulk of the tumor cells and fails to target the more aggressive cancer initiating cells (CIC) or cancer stem cells (CSC)
The chemoresistance of CSC is associated with expression of the membrane efflux transporter ABCG2 [27,41,42], which has been found to be upregulated in CSC from primary ovarian tumors and in both murine and human ovarian cancer cell lines [27,40,43]
Summary
Ovarian cancer is the fifth leading cause of cancer deaths in women and is the most lethal of the gynecological malignancies [1,2]. Several attempts have been made to find novel serum tumor markers of early-stage ovarian cancer, including measurements of soluble epidermal growth factor receptor (sEGFR) [17,18], soluble cytokeratin 19 fragments [19], serum human kallikreins [20,21,22,23] and serum vascular endothelial growth factor (VEGF) [24,25] Most of these biomarkers are limited to advanced stage or metastatic disease and are, not sufficiently sensitive for early-stage ovarian cancer screening and diagnosis. Doi:10.4172/2155-9929.S2-004 survival times as low as 24 months post diagnosis [1,6,7,8,26] Such poor prognosis seems to result from chemotherapy treatment that targets only the bulk of the tumor cells and fails to target the more aggressive cancer initiating cells (CIC) or cancer stem cells (CSC). This process most likely causes the occurrence of more aggressive tumors that are resistant to therapy (Figure 1) [27,28,29]
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