Forscherdatenbank

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Prof. Dr. Pauline Wimberger

Dresden
Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Fetscherstr. 74

01307 Dresden

Programme

Exploitation of Oncogenic Mechanisms (EOM)

Molecular Diagnostics, Early Detection, and Biomarker Development (MDEB)

Molecularly Targeted Therapy (MTT)

Übersicht

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 and we focus 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 predictor 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.

DKTK Junior Group Leader for Cancer Systems Biology

Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance. 

Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.