Proteomics for Cancer Diagnosis Cancer Recurrence Prediction and Personalized Cancer Therapy Monitoring

Early diagnosis of ovarian cancer has been shown to yield cure rates of 95%, whereas late-stage discovery results in a cure rate of only 35% (94,95). A novel biomarker for early diagnosis of ovarian cancer is critical because the conventional biomarker CA-125 is relatively insensitive for early-stage detection of ovarian cancer (96). Using mass-spec-trometry-based proteomics approach, Petricoin et al. has achieved a breakthrough in identifying distinctive serum protein pattern "fingerprints" to discriminate ovarian cancer patient from normal with 100% sensitivity and 95% specificity, which was improved to 100% sensitivity and 100% specificity, respectively, by a more sophisticated bioinfor-matic approach (27,97). This result showed the emergence of an accurate yet cost-effective, real-time, noninvasiveness proteomic method for early-stage detection of ovarian cancer. Similar proteomic techniques have also been developed for other cancers, including prostate, breast, lung, and colon cancers (29-32,98-100).

Clinical trials sponsored by the National Cancer Institute (NCI) are ongoing for further assessment and validation of proteomic technology in diagnosing and staging ovarian cancer for regulatory approval (101,102). In parallel, pilot studies are underway to evaluate proteomic technology for predicting the recurrence of epithelial ovarian cancer after first remission, selecting appropriate therapy regimens, and identifying patient subpopulations that will respond to therapy.

Proteomics can also be used as a tool to understand cancer drug function. Gleevec (imatinib mesylate) is a targeted therapy, designed to interfere with the function of two tyrosine kinases, c-kit and the PDGF (platelet-derived growth factor) receptor, suggesting Gleevec as a potential therapy for patients with ovarian cancer (103). In the much anticipated phase II trial to evaluate the effectiveness of Gleevec and determine whether it affects the predicted pathways in cancer cells, biopsies of patients' tumors will be taken prior to and after treatment. The proteomic pattern will then be measured and correlated to clinical response to treatment for a better understanding ofthe specific ways that Gleevec affects tumor cells. The result ofthis study can also be used to help physicians determine early in treatment whether Gleevec is working effectively for an individual cancer patient, suggesting an approach to tailor treatment to individual patients. Similar studies are undergoing at NCI to use the proteomic approach for the monitoring of key pathways influenced by the molecularly targeted drugs Herceptin® and Iressa®.

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