Project Overview and Scientific Background

Gastric cancer is estimated to be the fourth most common cancer and second leading cause of death from cancer worldwide. Treatment options for gastric cancer patients include surgery, chemotherapy and radiation therapy; however, the overall survival rate remains unsatisfactory and new treatment options are urgently required. Novel drugs targeting members of a family of receptor tyrosine kinases including HER2 and EGFR have shown mixed success in clinical trials. While the HER2 antibody trastuzumab has been approved for gastric cancer treatment, the EGFR antibody cetuximab recently failed in a phase III clinical trial as a gastric cancer treatment, but is approved for colorectal cancer treatment.

Supported by Germany's Federal Ministry of Education and Research (BMBF), the SYS-Stomach consortium aims to answer clinical questions about predictive factors regarding gastric carcinoma HER2-positive trastuzumab responders, cetuximab responders, and specific differences in reaction to HER2 and EGFR targeted treatments.

The SYS-Stomach project builds on the knowledge gained regarding cetuximab in an earlier BMBF project, CANCERMOTISYS, and will further systematically characterize gastric cancer cell lines in response to treatment with cetuximab as well as trastuzumab. The effects of the treatment will be determined both on the phenotypic level (motility and invasion assays) and on the molecular level (transcriptomics, epigenomics, proteomics). Time-resolved effects of the treatment on the EGFR and HER2 signaling pathways will be monitored. Candidate response and risk factors to targeted therapy will be validated in vitro and in vivo.

References

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