Patient Derived Tumoroids of High Grade Neuroendocrine Neoplasms for More Personalized Therapies

Overview

Journal NPJ Precis Oncol

Publisher Springer Nature

Specialty Oncology

Date 2024 Mar 1

PMID 38429350

Authors

Simon L April-Monn

Philipp Kirchner

Katharina Detjen

Konstantin Brautigam

Mafalda A Trippel

Tobias Grob

Cyril Statzer

Renaud S Maire

Attila Kollar

Aziz Chouchane

Catarina A Kunze

David Horst

Martin C Sadowski

Jorg Schrader

Ilaria Marinoni

Bertram Wiedenmann

Aurel Perren

Affiliations

Soon will be listed here.

Abstract

There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients' clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses.PD tumoroids recapitulated biological key features of high-grade GEP-NEN and mimicked clinical response to cisplatin and temozolomide ex vivo. When we investigated treatment-induced adaptive stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5 A and interferon-beta, which act synergistically in combination with cisplatin. Since ex vivo drug response in PD tumoroids matched clinical patient responses to standard-of-care chemotherapeutics for GEP-NEN, our rapid and functional precision oncology approach could expand personalized therapeutic options for patients with advanced high-grade GEP-NEN.

Citing Articles

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