Despite decades of research and evolving treatment modalities, survival among patients with epithelial ovarian cancer has improved only incrementally. During this same period, the development of biologically targeted therapeutics has improved survival for patients with diverse malignancies. Many of these new drugs target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of tyrosine kinases, which play a major role in the etiology and progression of many carcinomas, including epithelial ovarian cancer. While several HER-targeted therapeutics are US FDA approved for the treatment of various malignancies, none have gained approval for the treatment of ovarian cancer. Here, we review the published literature on HER-targeted therapeutics for the treatment of ovarian cancer, including novel HER-targeted therapeutics in various stages of clinical development, as well as the challenges that have limited the use of these inhibitors in clinical settings.
BackgroundWe evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines.Materials and methodsTrop-2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium-release assays against UMMT and OMMT cells.ResultsTrop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2.ConclusionTrop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2.
OBJECTIVE. This study assessed the clinical impact of pelvic MRI performed after the diagnosis of an indeterminate pelvic mass on ultrasound or CT. MATERIALS AND METHODS. The radiologic records of 567 patients who underwent pelvic MRI at our hospital from 2004 to 2006 were reviewed. Of these patients, 214 patients underwent pelvic MRI for evaluation of a gynecologic mass detected on a preceding ultrasound or CT examination; this group of patients constituted the basis of our study. The imaging and clinical records from the database were used for our analysis. The medical records were reviewed for the impact of the radiologic findings on patient treatment, and the results were tabulated for the findings of the first modality, whether the first modality provided a diagnosis, what management plan would be made according to the first modality, and what management plan would be made as a result of the MRI. The adequacy of the imaging study was assessed on the basis of either obtaining an accurate exact diagnosis or ascertaining at the minimum whether the mass was benign or malignant. Further endpoints included specificity and sensitivity of the individual modalities in the diagnosis of a specific gynecologic mass and whether clinical management was altered. Exact binomial CIs were computed for individual proportions. RESULTS. The clinical management of the patient was altered as a result of MRI in 77% of the cases (CI = 0.70-0.82). Surgery was avoided in 36% (CI = 0.29-0.43), and surgery was changed to a more appropriate method (laparoscopy vs laparotomy, involvement or not of a gynecologic oncologist) in an additional 17% (CI = 0.12-0.23). CONCLUSION. Without having undergone MRI, many of the women and girls in this study would have undergone unnecessary surgery; a more costly type of surgery; or long-term follow-up with the associated financial costs, personal and physical costs, and mental costs from the resultant anxiety of an unresolved indeterminate mass.
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