Researcher Database
Dr. Carsten Grötzinger
Campus Virchow-Klinikum Charité - Universitätsmedizin Berlin
Augustenburger Platz 1
13353 Berlin
Program
Radiation Oncology and Imaging (ROI)
Summary
Transcriptional profiling of G3 neuroendocrine tumors
Background: Poorly differentiated NEC account for 10-20% of all malignant digestive neuroendocrine neoplasias (NEN). Up to 85% of patients present with metastases and hence, survival is poor in NEC, ranging from 38 months for patients with localized disease to 5 months in the metastatic setting. NEC are currently defined by the WHO 2010 classification as poorly differentiated NEN with Ki-67 >20% and hence G3. Increasing evidence suggests that G3 NEN are not a homogenous entity and can be further subclassified into biologically relevant subgroups. A separation based on the proliferative index (Ki-67 >55%) was shown to have clinical implications regarding response to chemotherapy and prognosis. More recent publications show that morphological differentiation and Ki-67 are able to separate prognostic groups among G3 cases. Aims: This study is designed to pursue the following aims: 1. Elucidation of the genomic/transcriptomic heterogeneity in high-grade GEP-NET and NEC and molecular classification of these tumors. 2. Identification of transcriptomic profiles and pathway modifications with potential relevance for therapeutic patient stratification. 3. Discovery of novel cell-surface targets (based on transcriptomic profile, fusion genes, splice variants) suitable for PET imaging and peptide radioreceptor therapy (PRRT). Strategy: To pursue these goals, next generation RNA sequencing of tumor and normal tissue samples at the DKFZ core facility is performed. Bioinformatic analysis is carried out in collaboration with other groups within DKTK Berlin.
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.