Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response

Abstract

Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis. Seven PDAC tissues were cultured and subsequently treated with indole-3-pyruvic acid (IPA). IPA, which is known as an agonist of the aryl hydrocarbon receptor (AHR) pathway, has antioxidant properties. Genome-wide transcriptome sequencing analysis revealed activation of AHR pathway genes (CYP1A1 and CYP1B1, p ≤ 0.05). Additionally, significant upregulation of AHR repressor genes AHRR and TiPARP was also observed (p ≤ 0.05), which is indicative of the negative feedback loop activation of AHR pathway signaling. The overall transcriptomic response to IPA indicated that the tissues are biologically active and respond accordingly to exogenous treatment. Cell culture analysis confirmed the significant induction of selected AHR genes by IPA. A morphological examination of the paraffin-embedded formalin-fixed tissue did not show obvious signs of IPA treatment related to tumor cell damage. This study is a proof of concept that ex vivo patient-derived tissue models offer a valuable tool in precision medicine to monitor the effect of personalized treatments.

Pancreatic cancer environment: from patient-derived models to single-cell omics

“…An investigation elucidated the application of the aryl hydrocarbon receptor (AHR) signaling pathway by indole-3-propionic acid (IPA) in an ex vivo tissue explant PC model and identified AHR signaling genes and quantified at the transcriptome level. 51 PDX tissues, isolated from mice, can be utilized for the cultivation of patient-derived xenograft explants (PDXEs). The PDX tumor tissue of mice was isolated, cultured in vitro , and subsequently utilized in the experiment.…”

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services

“…To this day, this is the closest human cancer model system to strengthen preclinical drug discovery and treatment decision in oncology [34][35][36][37][38]. In the past, tumor tissue slices have been used to study culture conditions and drug response assays with antineoplastic agents [8,35,39,40], analyze metastatic processes [41], and investigate new therapeutic or diagnostic strategies [42][43][44]. Other applications include studies on the regulation of tumor markers [45], the immune microenvironment [46], gene therapy [47,48], the antineoplastic potential of various agents [24,49,50], and drug sensitivity using electrochemical sensors [51], among others.…”