[Establishment of a living biobank : Improved guidance of precision cancer care with in vitro and in vivo cancer models].
C Pauli, H Moch, M A Rubin
Author Information
C Pauli: Institut für Pathologie und Molekularpathologie, UniversitätsSpital Zürich, Schmelzbergstrasse 12, 8091, Zürich, Schweiz. chantal.pauli@usz.ch.
H Moch: Institut für Pathologie und Molekularpathologie, UniversitätsSpital Zürich, Schmelzbergstrasse 12, 8091, Zürich, Schweiz.
M A Rubin: Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, USA.
BACKGROUND: Precision oncology is a clinical approach aimed towards tailoring treatment strategies for patients based on the genetic profile of each patient's cancer. The integration of a living biobank, consisting of patient-derived tumor organoids and PDXs, with next generation sequencing approaches and high-throughput drug screening help to guide clinical decision-making and clinical trial development. METHODS: Tumor organoids derived from fresh tumor samples were used for in vitro and in vivo high-throughput drug testing. RESULTS: Over a period of two years we established 56 in vitro tumor organoids and 19 in vivo xenografts from 18 different solid tumor types. Tumor morphology and molecular profiles show good concordance between the in vitro and in vivo models compared to their native tumor. High-throughput drug screening (up to 160 drugs) has been tested on eight tumor organoid lines. Seven of them underwent an additional combination drug screen. We nominated several targeted small molecules and novel combinations that have been validated in corresponding xenograft models. CONCLUSION: This precision medicine approach outlines the integration of genomic data with drug screening from personalized preclinical cancer models to guide precision cancer care. It also fuels next generation research and has been implemented for clinical trial development.
