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Department of Gynecology and Obstetrics

The research group “Molecular Gynecologic Oncology” (Department of Gynecology and Obstetrics, Technische Universität Dresden) with Prof. Wimberger as Head of Department and Dr. Kuhlmann as Head of Laboratory performs clinical translational Research. Our main focus is on the identification of predictive/prognostic biomarkers and innovative targeted therapies for gynecologic malignancies, with the main interest in ovarian and breast cancer. For biomarker identification, we perform molecular biological characterization of the primary tumor and correlate these findings with the patient’s clinicopathological data. A particular focus is the analysis of VEGF-receptors and their potential relevance as prognostic biomarkers or as response predictors for antiangiogenic therapy [1]. 

Moreover, our aim is the identification of blood-based biomarkers for prognosis stratification or for predicting response to platinum-based chemotherapy or other targeted therapies, such as Bevacizumab or PARP-inhibitors. We have expertise in very sensitive methods for the enrichment and molecular characterization of circulating tumor cells (CTCs) from the blood of breast and ovarian cancer patients. In this context, we recently identified ERCC1-expressing CTCs as an independent predictor for primary platinum-resistance in ovarian cancer patients [2]. Moreover, with regard to “liquid biopsy” approaches, we are interested in the characterization of circulating cell free nucleic acids, such as cell free tumor DNA (ctDNA) or circulating small RNAs by Next-Generation-Sequencing. In this regard, we recently described a circulating small RNA fragment in serum of ovarian cancer patients, which could be used for monitoring platinum-based chemotherapy and for identifying a subgroup of patients with poor prognosis [3]. We also have expertise in the detection and molecular characterization of disseminated tumor cells (DTCs) in the bone marrow of breast and ovarian cancer patients and we offer DTC-positive breast cancer patients a preventive bisphosphonate treatment, which has previously been shown to eradicate DTCs in the bone marrow and to improve survival.

Apart from our biomarker studies, we are interested in innovative targeted therapy approaches for ovarian cancer patients. For this purpose, we established several biochemical cell-based screening assays, for the in vitro characterization of novel therapeutic agents. Furthermore, we are currently designing a preclinical mouse model for platinum-resistant or BRCA1-deficient ovarian cancer, in order to further analyze potential clinical utility of novel drug candidates, according to clinically relevant question. Our particular focus in this context is the identification of novel sensitizer compounds for platinum-based chemotherapy in platinum-resistant ovarian cancer.

The effect of the triazene compound CT913 on ovarian cancer cells in vitro and its synergistic interaction with the PARP-inhibitor olaparib.
Wichmann C, Klotz DM, Zeiler HJ, Hilger RA, Grützmann K, Krüger A, Aust D, Wimberger P, Kuhlmann JD.Gynecol Oncol. 2020 Dec;159(3):850-859. doi: 10.1016/j.ygyno.2020.09.018. Epub 2020 Sep 23.PMID: 32980128

Diphenhydramine increases the therapeutic window for platinum drugs by simultaneously sensitizing tumor cells and protecting normal cells.
Melnikova M, Wauer US, Mendus D, Hilger RA, Oliver TG, Mercer K, Gohlke BO, Erdmann K, Niederacher D, Neubauer H, Buderath P, Wimberger P, Kuhlmann JD, Thomale J.Mol Oncol. 2020 Apr;14(4):686-703. doi: 10.1002/1878-0261.12648. Epub 2020 Mar 10.PMID: 32037720 Free PMC article.

Serum calretinin as an independent predictor for platinum resistance and prognosis in ovarian cancer.
Link T, Passek S, Wimberger P, Frank K, Vassileva YD, Kramer M, Kuhlmann JD.Int J Cancer. 2020 May 1;146(9):2608-2618. doi: 10.1002/ijc.32676. Epub 2019 Nov 6.PMID: 31509615

Clinical relevance of circulating MACC1 and S100A4 transcripts for ovarian cancer.
Link T, Kuhlmann JD, Kobelt D, Herrmann P, Vassileva YD, Kramer M, Frank K, Göckenjan M, Wimberger P, Stein U.Mol Oncol. 2019 May;13(5):1268-1279. doi: 10.1002/1878-0261.12484. Epub 2019 Apr 15.PMID: 30927479 Free PMC article. Clinical Trial.

EMT-like circulating tumor cells in ovarian cancer patients are enriched by platinum-based chemotherapy.
Chebouti I, Kasimir-Bauer S, Buderath P, Wimberger P, Hauch S, Kimmig R, Kuhlmann JD.Oncotarget. 2017 Jul 25;8(30):48820-48831. doi: 10.18632/oncotarget.16179.PMID: 28415744 Free PMC article.