Peschke, K., Jakubowsky, H., Schafer, A., Maurer, C., Lange, S., Orben, F., Bernad, R., Harder, F. N., Eiber, M., Ollinger, R., Steiger, K., Schlitter, M., Weichert, W., Mayr, U., Phillip, V., Schlag, C., Schmid, R. M., Braren, R. F., Kong, B., Demir, I. E., Friess, H., Rad, R., Saur, D., Schneider, G., and Reichert, M. (2022). EMBO Mol Med 14, e14876. doi: 10.15252/emmm.202114876

Abstract: 

Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.