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Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology.

ABSTRACT: One of the major challenges in using pancreatic cancer patient-derived organoids (PDOs) in precision oncology is the time from biopsy to functional characterization. This is particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting in specimens with limited tumor cell yield. Here, we tested conditioned media of individual PDOs for cell-free DNA to detect driver mutations already early on during the expansion process to accelerate the genetic characterization of PDOs as well as subsequent functional testing. Importantly, genetic alterations detected in the PDO supernatant, collected as early as 72 hours after biopsy, recapitulate the mutational profile of the primary tumor, indicating suitability of this approach to subject PDOs to drug testing in a reduced time frame. In addition, we demonstrated that this workflow was practicable, even in patients for whom the amount of tumor material was not sufficient for molecular characterization by established means. Together, our findings demonstrate that generating PDOs from very limited biopsy material permits molecular profiling and drug testing. With our approach, this can be achieved in a rapid and feasible fashion with broad implications in clinical practice.

SUBMITTER: Dantes Z

PROVIDER: S-EPMC7455062 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology.

Dantes Zahra Z Yen Hsi-Yu HY Pfarr Nicole N Winter Christof C Steiger Katja K Muckenhuber Alexander A Hennig Alexander A Lange Sebastian S Engleitner Thomas T Öllinger Rupert R Maresch Roman R Orben Felix F Heid Irina I Kaissis Georgios G Shi Kuangyu K Topping Geoffrey G Stögbauer Fabian F Wirth Matthias M Peschke Katja K Papargyriou Aristeidis A Rezaee-Oghazi Massoud M Feldmann Karin K Schäfer Arlett Pg AP Ranjan Raphela R Lubeseder-Martellato Clara C Stange Daniel E DE Welsch Thilo T Martignoni Marc M Ceyhan Güralp O GO Friess Helmut H Herner Alexander A Liotta Lucia L Treiber Matthias M von Figura Guido G Abdelhafez Mohamed M Klare Peter P Schlag Christoph C Algül Hana H Siveke Jens J Braren Rickmer R Weirich Gregor G Weichert Wilko W Saur Dieter D Rad Roland R Schmid Roland M RM Schneider Günter G Reichert Maximilian M

JCI insight 20200806 15

One of the major challenges in using pancreatic cancer patient-derived organoids (PDOs) in precision oncology is the time from biopsy to functional characterization. This is particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting in specimens with limited tumor cell yield. Here, we tested conditioned media of individual PDOs for cell-free DNA to detect driver mutations already early on during the expansion process to accelerate the genetic characte ...[more]

PMID: 32614802

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Project description:BackgroundHigh grade serous ovarian cancer (HGSOC) is among the deadliest human cancers and its prognosis remains extremely poor. Tumor heterogeneity and rapid acquisition of resistance to conventional chemotherapeutic approaches strongly contribute to poor outcome of patients. The clinical landscape of HGSOC has been radically transformed since the advent of targeted therapies in the last decade. Nevertheless, the lack of predictive biomarkers informing on the differential clinical benefit in select subgroups, and allowing patient-centric approaches, currently limits the efficacy of these novel therapies. Thus, rational selection of the best possible treatment for each patient represents a clinical priority in order to improve outcome, while limiting undesirable effects.Main bodyIn this review, we describe the state of the art and the unmet needs in HGSOC management, illustrate the treatment options that are available and the biomarkers that are currently employed to orient clinical decisions. We also describe the ongoing clinical trials that are testing new therapeutic approaches for HGSOC. Next, we introduce the organoid technology as a promising, expanding strategy to study cancer and to develop personalized therapeutic approaches. In particular, we discuss recent studies that have characterized the translational potential of Patient's Derived Organoids (PDOs) to inform on drug sensitivity of HGSOC patients.ConclusionsPDOs can predict the response of patients to treatments and may therefore guide therapeutic decisions. Although preliminary results appear encouraging, organoids still need to be generated and expanded efficiently to enable drug screening in a clinically meaningful time window. A new generation of clinical trials based on the organoid technology should guarantee tailored approaches to ovarian cancer management, as it is now clear that the one-size-fits-all approach cannot lead to efficient and meaningful therapeutic advancements.

Dataset Information

Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology.

Publications

Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology.

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