In this work, miniature organs mimicking the tissue of patients with oesophageal cancer were developed by sampling cells from these patients' tumours and growing them in a dish.
We showed that these 3D models of this cancer (called "organoids") can be used effectively in order to study the evolution of this cancer and to test various drug combinations that could be applied in the clinic. By sequencing the DNA of these organoids and that of the respective tumours of origin, we found that the mutations that have arisen during cancer development in the respective patients are captured with high fidelity in the 3D model. Subpopulations of cancer cells within this 3D model were shown to evolve following a natural selection processes, which can be informative for understanding responses to various treatments and patient relapse. Finally, through extensive drug screening we found that these 3D oesophageal cancer models responded well to inhibitors of a class of molecules called receptor tyrosine kinases, with important roles in cell growth signalling. This system can be a useful resource for the scientific community for quick experimental validation of hypotheses in oesophageal cancer, and some of the findings reported in this paper may be further exploited in the clinic for the treatment of this disease.
Read full paper: Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics
Authors: Xiaodun Li, Hayley E. Francies, Maria Secrier, Juliane Perner, Ahmad Miremadi, Núria Galeano-Dalmau, William J. Barendt, Laura Letchford, Genevieve M. Leyden, Emma K. Goffin, Andrew Barthorpe, Howard Lightfoot, Elisabeth Chen, James Gilbert, Ayesha Noorani, Ginny Devonshire, Lawrence Bower, Amber Grantham, Shona MacRae, Nicola Grehan, David C. Wedge, Rebecca C. Fitzgerald & Mathew J. Garnett