Cancer tissue model to identify potential marker proteins for prediction of drug efficacy in individual tumors

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3147 Model systems which allow studying drug effects on primary tumour cells within different compartments of an individual tumour ex vivo provide a great advance for research on both response prediction and investigation of efficacy of novel treatment strategies. We recently established a tumor tissue model that allows short term culture of freshly excised breast cancer tissues. This model system allows the determination of cell viability, cell death, proliferation, and expression of surface molecules in different compartments of cancer tissues over a time period of at least 4 days (van der Kuip et al., BMC Cancer, 2006). We now expanded this system on other tumor entities such as colon carcinoma, lung carcinoma, ovary carcinoma, and lung metastasis. In total we cultivated tissue slices from 78 tumors (breast: 37; colon: 9; lung: 19; ovary: 4; lung metastasis: 9). With the exception of tissues from 2 ovaries and 2 mucinous breast carcinomas, which turned out to be too soft to cut, and tissues from 1 colon, 2 breast, and 2 ovary cancers, which were contaminated with bacteria, all tissue types were successfully cultivated: cells remained viable for at least 4 days within their tissue environment. By treating different tissue slices with different drugs/drug combinations, this model system allows a rapid assessment of drug efficacy in different tumor entities. For the identification of potential predicitive markers for treatment response, we started to investigate the influence of erlotinib in tissues from primary lung cancers and metastasis on protein expression by 2D gel electrophoresis and mass spectrometry. In lung metastases treated with 2µM erlotinib for 72 hours proliferation was significantly inhibited and initially 30 proteins were found to be changed including proliferation and tumour associated factors. In conclusion, we describe a tissue culture method which allows the assessment of drug efficacy and proteomic analysis within individual cancer tissues from different origin. This method has significant advantages for the identification of potential predictive markers for efficacy of clinically significant drugs in tissues from individual tumors.