The use of patient-derived 3D cell cultures in pre-clinical research

5^th World Congress on Cancer Therapy

September 28-30, 2015 Atlanta, USA

Christian RA Regenbrecht

CPO � cellular phenomics & oncology GmbH, Germany

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

Together with our partner company EPO we have generated patient-derived 3D (PD3D�) cell culture models and corresponding xenografts from more than 120 patients with primary or metastatic cancers of various origins. Although early diagnosis and molecular characterization of cancer has improved significantly, methods for rapid and cost-effective prediction of an optimal and individualized treatment are still missed. We present an experimental pipeline combining molecular genotyping and experimental drug testing for the individual patient. Starting from Matrigel-based Patient-derived three-dimensional PD3D� cell cultures, we were able to establish numerous long-term PD3D� cell cultures suitable as models for basic and translational research. Immunohistochemistry analyses demonstrated, that our in vitro cultures preserve an in vivo-like architecture, preventing tumor cells from differentiating and allowing the investigation of intra-tumor heterogeneity and cancer stem cell-like sub-populations. To interrogate the mutation status of selected clinically relevant oncogenes and tumor suppressors in PD3D� cultures, we applied cost-efficient benchtop sequencing and show the preservation of putative driver mutations found in the original tumor. IC50 data generated by automated 384-well based dose-response experiments with approved drugs are then used to link individual genotypes with drug sensitivity phenotypes. These drug sensitivity profiles serve as a source of comparison and complementation to drug response data of the corresponding in vivo PDX models or even patients, where applicable. These wet-lab data, combined with in vivo and clinical data, will serve as a basis for both, early phase drug development including companion diagnostics to new predictors for tailored therapies.

Biography :

Email: christian.regenbrecht@cpo-berlin.com