Clinical validation of response and resistance factor candidates to targeted therapy in gastric cancer
Gastric cancer is an aggressive cancer with a poor prognosis. Cancer cells are as endogenous cells not well recognized of our immune system and therefore not eliminated. Often the metabolism and the surface of the cancer cell are different compared to healthy neighbouring cells. Against these altered surfaces targeted therapies have been developed in recent years that mark cancer cells and make these visible to the immune system. In addition same drugs can block signal transduction pathways from the surface to the cell interior and inhibit the aggressiveness and the further growth of the tumor cells.
In 10-20% of the tissue of patients suffering gastric cancer proteins are overexpressed, which belong to the epidermal growth factor receptor (EGFR) family, stimulating cell proliferation and suppressing cell death. Against these receptors targeted therapies have been developed and approved for different tumor types.
If targeted therapy trastuzumab in addition to conventional chemotherapy is used treating HER2 / neu positive gastric cancer patients, response and life expectancy improve. Unfortunately, some of the tumors are trastuzumab resistant. And initial responsive tumors develop during treatment resistance mechanisms and begin to grow again. Therefore, we want to examine tissue samples of patients on biomarkers that can predict a response or resistance to the targeted therapy. The most promising biomarkers are developed in laboratory experiments of the consortium and subsequently validated in patient samples.
There have already been collected tissue samples in clinical studies. Furthermore, tissue samples and treatment data of patients with HER2 / neu overexpression is needed for reliable and statistically meaningful results.
This is done by a non-interventional study called “VARIANZ” already approved by the leading Ethics Committee at the Medical Faculty of the University of Leipzig. The tissue and treatment data obtained in the VARIANZ study are basis for the exploration of biomarkers for prediction of response or resistance of target therapy used in treatment of gastric cancer.