Abstract

Biorespositories of formalin-fixed and paraffin-embedded (FFPE) or fresh frozen human tissues from malignant diseases generated as integral part of the diagnostic workup in many pathology departments have been pivotal resources for translational cancer studies. However, such tissue biobanks have traditionally contained only non-viable specimens and thus cannot enable functional assays for the discovery and validation of therapeutic targets or the assessment of drug responses and resistance to treatment. To overcome these limitations, we have developed a next-generation comprehensive biobanking platform that includes the generation of patient-derived in vitro cell models from colorectal, pancreatic and kidney cancers among others. As such patient-derived cell (PDC) models retain important features of the original human tumors, they have emerged as relevant tools for more dynamic clinical and experimental analyses of cancer. Here, we describe details of the complex processes of acquisition and processing of patient-derived samples, propagation, annotation, characterization and distribution of resulting cell models and emphasize the requirements of quality assurance, organizational considerations and investment into resources. Taken together, we show how clinical tissue collections can be taken to the next level thus promising major new opportunities for understanding and treating cancer in the context of precision medicine.

Highlights

  • Despite significant progress made in understanding and treating cancer in the last decades, this disease is still one of the leading causes of mortality worldwide (Siegel et al, 2016)

  • The comprehensive, tripartite biobanking strategy of collecting formalin-fixed and paraffin-embedded (FFPE), fresh frozen and patient-derived living cells we have described here offers a toolkit for addressing numerous questions in current and future basic, translational and clinical research

  • It is important to note that growth conditions are major influencing factors during propagation of patientderived cell (PDC) models as they impact on cellular processes such as replication and cell survival as well as on the genotypic and phenotypic heterogeneity of cell subpopulations

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Summary

INTRODUCTION

Despite significant progress made in understanding and treating cancer in the last decades, this disease is still one of the leading causes of mortality worldwide (Siegel et al, 2016). At the time when we started to develop our nextgeneration biobanking strategy, a suitable documentation tool for many aspects of living cell biobanking was not readily available and we developed a dedicated, comprehensive biobanking IT infrastructure (Figure 2D) This infrastructure was designed to interface with the clinical IT management systems and allows sample annotation with relevant demographic, pre-analytical and diagnostic information. The storage locations of viably frozen cells and their derivatives (DNA, RNA, protein extracts, etc.) can be tracked and since all records have been de-identified the dedicated biobanking databases for fresh frozen tissue and PDC models can be opened up for external researchers aiming to select a study cohort from the available samples In this database sample distribution is documented enabling us to follow-up on data that was generated by external investigators (Figure 2D). In order to demonstrate such value, our ongoing endeavors are directed toward sustaining and expanding our living cell biobank workflow alongside the traditional tumor tissue biorepository for future cancer research and clinical application

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