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Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion
Published on: July 6, 2022
Preclinical models of esophageal adenocarcinoma for drug development
David S Liu1,2,3, Cuong P Duong2,4, Wayne A Phillips1,2,3,4
1Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
Abstract:
The advent of multi-omic profiling of tumors, together with the increasing affordability of high-throughput drug screening programs, has helped usher in a new era of molecular targeted therapies for many solid malignancies. However, there has been limited success in esophageal adenocarcinoma. Until recently, preclinical drug development for this cancer has been largely limited to a small number of cell line models. Now, the increasing availability of patient-derived xenografts and novel metastatic models are helping to bridge the gap between scientific discovery and patient care. These platforms are valuable adjuncts for drug testing. Nevertheless, further work is required to develop systems that model the tumor microenvironment, including cancer cell interactions with the immune system, which will be particularly relevant for the translation of novel immunotherapies for esophageal adenocarcinoma.
Insights
Advancements in multi-omic profiling and drug screening enable targeted therapies for solid tumors. New esophageal adenocarcinoma models improve preclinical drug development, but tumor microenvironment modeling is needed for immunotherapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Molecular targeted therapies have advanced cancer treatment for many solid tumors.
- Esophageal adenocarcinoma has seen limited success with targeted therapies.
- Preclinical drug development was previously restricted to few cell line models.
Purpose of the Study:
- To review the progress and challenges in preclinical drug development for esophageal adenocarcinoma.
- To highlight the role of novel preclinical models in advancing targeted therapies.
- To identify future directions for improving drug testing platforms.
Main Methods:
- Review of current literature on multi-omic profiling and high-throughput drug screening.
- Analysis of the utility of patient-derived xenografts and metastatic models.
- Discussion of the limitations of existing models for tumor microenvironment representation.
Main Results:
- Multi-omic profiling and drug screening have accelerated targeted therapy development.
- Patient-derived xenografts and novel metastatic models enhance preclinical research for esophageal adenocarcinoma.
- Existing models do not adequately represent the tumor microenvironment and immune interactions.
Conclusions:
- Novel preclinical models are crucial for advancing esophageal adenocarcinoma treatment.
- Further development of models simulating the tumor microenvironment is essential.
- Translating immunotherapies for esophageal adenocarcinoma requires improved preclinical systems.

