Abstract LB-35: Living biobank of cancer organoids for drug development and screening

Abstract

Abstract Future cancer therapy will rely on treatment with drugs that are specific for individual tumours and patients. However, predicting clinical responses from genomic data remains highly challenging. Recently, systematic screens utilizing large panels of tumor cell lines have been used to correlate drug sensitivity with tumor genotype to identify predictive genomic markers of drug response. However, tumour cell lines have several drawbacks including being of limited genetic diversity; pre-clinical models that are more representative of the ‘natural’ mutational diversity of cancer are urgently required. The Clevers lab recently developed methods for long-term culture of human primary tissues and cancers (‘organoids’). By establishing a large collection of tumour-specific organoids, the genetic spectrum of tumours can be captured as a pre-clinical model. This will allow stratification of tumours based on their genomic footprint and drug sensitivity, and may reveal correlations between drug sensitivity and this footprint. We have now established the organoid technology and the first biobank of Colon, Pancreas, and Lung primary carcinomas and metastasis. Importantly, whole genome sequencing of the initial tumour material and long term cultures demonstrate that, similar to healthy organoids, also tumour organoids are stable. The first screens with sets of drugs that are clinically available shows that the organoids respond as would be predicted by their sequence analysis, such as KRAS mutant organoids not responding to the EGFR inhibitor Cetuximab. We do however find patient specific differences which points to a promising role for organoids in drug development, patient stratification and possibly diagnosis. Finally, genetic analysis has indicated that we are efficiently generating organoids of the full range of genetic alterations previously identified in patients for these tumour types, including specific genotypes that are poorly or not represented in any other in vitro model at the moment. Citation Format: Robert G.J. Vries, Hans Clevers. Living biobank of cancer organoids for drug development and screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-35. doi:10.1158/1538-7445.AM2014-LB-35