Screening for ovarian cancer: what are the optimal surrogate endpoints for clinical trials?
The inability to identify relevant markers for presymptomatic screening in early stage or "preinvasive" ovarian cancer has plagued investigators and clinicians facing the problems of early detection. The characteristic late stage of disease at initial presentation has hindered our understanding of the biologic progression and stepwise molecular alterations that result in ovarian carcinoma. To date, most screening studies have focused on identifying early anatomic changes using ultrasound or fluctuations in serum biomarkers such as CA-125. These screening methodologies have proven inadequate in both sensitivity and specificity for early stage ovarian cancer detection. Molecular analysis of ovarian carcinomas has revealed alterations in oncogenes and tumor suppressor genes associated with these tumors. The HER-2/neu oncogene, a member of the epidermal growth factor family, is amplified or overexpressed in approximately 25-30% of ovarian carcinomas. Significant data substantiate an important role for HER-2/neu in the pathophysiology of ovarian cancer. While potentially an attractive surrogate endpoint biomarker (SEB), serum HER-2/neu levels have not proven to be a useful screening modality. In response to the urgent need for improved early detection for ovarian cancer, our current research efforts include differential hybridization studies between normal and malignant ovarian epithelium to define potentially unique ovarian cancer antigens which may ultimately have utility; defining physical alterations that occur in malignant ovarian tissues using implanted telemetry systems; studies using positron emission tomography to detect changes in glucose metabolism between normal and malignant ovarian tissues; and screening studies using a 3-dimensional ultrasound unit to improve the accuracy of this technique in recognizing early neoplastic changes. By taking diverse approaches to tackle this problem, an improved understanding of ovarian carcinogenesis should translate into the identification of appropriate SEBs for early detection.
Karlan
B Y
BY
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, UCLA School of Medicine 90048, USA.
D014408:Biomarkers, Tumor / Q000032:analysis; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D011237:Predictive Value of Tests; D014463:Ultrasonography
D014408:Biomarkers, Tumor