SP 1

Systematic molecular and phenotypical characterization of gastric cancer cell lines

The overall research goal of the consortium is to identify response and resistance factors to targeted therapy with cetuximab or trastuzumab in gastric carcinoma using a systems medicine approach and to identify specific differences of the cells in the reaction to both treatment options. The research goal of the subproject is the characterization of gastric cancer cell lines in response to treatment with trastuzumab, corresponding data for cetuximab are available from the CANCERMOTISYS project. The effects of the treatment will be determined both on the phenotypic level (motility and invasion assays) as well as 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 resistance factors to targeted therapy will be validated in vitro.

 

Overview on the analysis of cellular motility
The focus of the phenotypic characterization of gastric cancer cell lines will be the comprehensive documentation of cellular motility in microscopic films obtained by time-lapse microscopy after activation or inhibition of the HER2 pathway, semi-automatic tracking and quantitative description of cellular movement.

The scientific concept is based on the observation that EGFR and HER2 pathways are involved in gastric cancer tumor progression and that both receptors serve as therapeutic targets. We hypothesize that the analysis of gastric cancer cell lines will enable the consortium to define candidate predictive biomarkers which will be validated both in cell lines (SP1) and gastric cancer patients (SP5, SP6).

The work is organized in four work-packages:
WP 1-3: We will provide experimental in vitro data to enable the construction of probabilistic molecular (SP2, SP3) and agent based cellular models (SP2, SP4) of gastric cancer cells.
WP 4: We will validate the predictive signature for gastric cancer treatment response and risk identified in subprojects SP2, SP3 and SP4.


Keywords: Gastric carcinoma, targeted tumor therapy, response and resistance factors, biomarker, trastuzumab, cetuximab