The potential and challenges of patient-derived organoids in guiding the multimodality treatment of upper gastrointestinal malignancies

Abstract

The incidence of adenocarcinoma at the gastrooesophageal junction increased over the last years. Curative treatment for patients with upper gastrointestinal (UGI) malignancies, such as oesophageal and gastric tumours, is challenging and requires a multidisciplinary approach. Radical surgical resection with complete lymphadenectomy is the cornerstone of UGI cancer treatment. Combined with peri-operative treatment (i.e. by applying CROSS, EOX or FLOT regimen), the survival is even better than with surgery alone. However, peri-operative treatment is not effective in all patients, and the most effective strategy is a topic of active debate, as is reflected by varying treatment guidelines between countries. UGI cancers are (epi)genetically highly heterogeneous. It is thus not likely that a uniform treatment will benefit all patients equally well. Over recent years, patient-derived organoids (PDOs) gained more and more interest as an in vitro prediction model that may assist as a diagnostic tool in the future to select and eventually optimize the best peri-operative treatments for each patient. PDOs can be derived from endoscopic tumour biopsies, which maintain heterogeneity in culture. They can be rapidly established and expanded in a relatively short time for in vitro drug screening experiments. This review summarizes the clinical and molecular aspects of oesophageal and gastric tumours, as well as the current progress and remaining challenges in the use of PDOs for drug and radiation screens.

From 2D to 3D Cancer Cell Models—The Enigmas of Drug Delivery Research

“…For example, a protocol to grow and maintain organoids derived from human endometrial cancer was recently described by Boretto et al [ 110 ]. This publication is a good example of how to create organoids from cells of cancer patient biopsies and highlights the potential of these in vitro models to develop personalized medicine [ 109 , 110 , 111 , 112 , 113 ]. Recently, Driehuis et al reported an overview of the different protocols for the generation of organoids from various cancer types, including a protocol to test the sensitivity of patient-derived organoids to specific cancer therapies [ 114 ].…”

“…The patient specificity makes organoids extremely popular in personalized medicine and drug screening tests. Immense breakthroughs have already been made by using these models in treatment response prediction tests [ 112 , 115 , 116 , 117 ]. Cancer organoids (or tumoroids), recapitulate the in vivo tissue heterogeneity, including the presence of a stem cell population [ 118 ].…”

“…Furthermore, it is the only model that allows the investigation of all the cell types present in a given organ. In line of this, at this moment, organoids are a hot-topic in the field of personalized medicine [ 112 , 115 , 116 , 117 ].…”

High content 3D imaging method for quantitative characterization of organoid development and phenotype

“…Beyond numerous biological challenges 6,7 , the organoid cultures also pose technological challenges, in terms of cell culture methods, characterization of transcriptomics, and imaging. In vivo organ development occurs in a biological environment that results in a highly stereotypical self-organization of cell arrangements.…”

Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy

“…By establishing models, which resemble the patient’s situation more closely, many research groups hope that the adequate therapy for the individual patient can be determined with a higher probability. Over the past years, patient-derived organoids (PDOs) from many different tumor types have been established and gained interest as a tool for drug screening ( 10 – 12 ).…”