Role of growth factor receptors and their downstream signaling pathways in the resistance or response of rectal adenocarcinoma to neoadjuvant radiochemotherapy

• Applicant: Professor Dr. Peter Burfeind
• Subject Area: General and Visceral Surgery
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 33996666

Growth factors and their receptors play a significant role in the regulation of cancer growth, tumor angiogenesis, and metastasis, which makes these molecules attractive for targeted therapies. Our recent studies have indicated that the insulin-like growth factor receptor (IGF-IR) together with the epidermal growth factor receptor (EGFR) are able to influence the cellular response of colorectal cancer (CRC) cells. Moreover, inhibition of both receptors has additive effects on proliferation reduction, cell death, and response to 5-fluorouracil (5-FU)-based radiochemotherapy (RCT). From these observations we speculate that the therapeutic efficacy can be even further enhanced by inhibition of more than two receptor tyrosine kinase (RTK) pathways. In this respect, the project aims to identify molecular mechanisms of growth factor receptor cross-talk in rectal adenocarcinomas in response to neoadjuvant therapy. The studies will be performed in established CRC cell lines, primary rectal cancer cell lines, xenotransplants of CRC cell lines, and biopsy material taken from rectal adenocarcinomas. The project will further investigate the mechanisms of resistance to IGF-IR and EGFR inhibitors, thereby identifying new potential therapeutic targets.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 179: Biological Basis of Individual Tumour Response in Patients with Rectal Cancer
• Participating Persons: Privatdozentin Dr. Silke Kaulfuß; Professor Dr. Jens-Gerd Scharf