New tumor markers: CA125 and beyond

University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
International Journal of Gynecological Cancer (Impact Factor: 1.95). 10/2005; 15 Suppl 3(Suppl 3):274-81. DOI: 10.1111/j.1525-1438.2005.00441.x
Source: PubMed

ABSTRACT A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase II trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer.

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    • "Today, the most commonly used combination is that in which CA-125 and imaging methods are used together (Ashrafgangooei and Rezaeezadeh, 2011). However, this combination is not sufficient for early diagnosis due to the low sensitivity of CA-125 and the cost of imaging methods (Bast et al., 2005). Therefore, development a new marker to increase the early detection rate is necessary. "
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    • "Among gynecologic malignancies, epithelial ovarian cancer (EOC) is the leading cause of death (Kohler et al., 2011). Most EOC cases are diagnosed at an advanced stage of the disease because the premalignant state is poorly understood and an efficient screening strategy is not presently available (Bast et al., 2005). Although improvements in primary treatment, often consisting of cytoreductive surgery and platinum-based chemotherapy, have been made, the majority of these patients continue to experience relapses and eventually die from the disease (Bookman, 2003; Bast et al., 2009). "
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    • "But neither of these tests are sufficiently sensitive or specific [4]. Recently, biomarkers such as CA125 and CA19-9 have been used to help in the early screening and diagnosis of ovarian cancer i.e. at a stage when it is the most treatable and before it has had a chance to grow and spread [5] [6] [7] [8]. CA125 is the most widely used tumor marker in ovarian cancer but its sensitivity and specificity are not ideal because the levels of this marker are raised to approximately 80% of all epithelial ovarian cancers (EOC) and in only 50% of stage I EOC. "
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