Background: Patient-derived tumor models passaged only a few times in vivo retain physical and molecular characteristics of human cancer and may prove essential in identifying disease biomarkers and drug targets in later stage development. Currently we have collected tumor tissue from chemo-naïve and pretreated patients and established and characterized a panel of low passage colorectal tumor models.

Methods: For each model, tissue was implanted into immune-deficient mice and once established, each model was confirmed by histologic analysis and linked with donor patient treatment and outcome data. Model characterization including mutation profiling and drug sensitivity studies were performed and results compared with clinical patient information; each model was evaluated with the EGFR inhibitor cetuximab and two standard clinical therapies FOLFOX and irinotecan and compared with patient's drug sensitivity before and after tissue sample collection. Single agent tumor growth inhibition was evaluated and study endpoints included mean control tumor volumes of approximately 1 cm3 or up to sixty days following treatment initiation.

Results: Eighteen low passage colorectal models have been established and characterized. KRAS mutations were identified in 44% of models and activating mutations identified in some models include: PI3KCA (6%), TP53 (33%) and BRAF (6%). In vivo response to FOLFOX and irinotecan correlated to ≥65% of donor patient outcome to these treatments. Cetuximab sensitivity did not fully correlate with Ras mutation status as 4/6 wildtype and 4/8 Ras demonstrated cetuximab sensitivity in these studies.

Conclusion: We have generated a panel of low passage colorectal tumor models with differential mutation status and drug sensitivity profiles. Expansion of this panel of patient-derived tumors is planned and should further enhance its utility in identifying agents potentially useful for treatment of colorectal cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B17.