Researchers searched for a gene signature that discriminate localised pancreatic ductal adenocarcinoma (PDAC) from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events.
[EMBO Molecular Medicine]
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Thibault, B., Ramos-Delgado, F., Pons-Tostivint, E., Therville, N., Cintas, C., Arcucci, S., Cassant-Sourdy, S., Reyes-Castellanos, G., Tosolini, M., Villard, A. V., Cayron, C., Baer, R., Bertrand-Michel, J., Pagan, D., Ferreira Da Mota, D., Yan, H., Falcomatà, C., Muscari, F., Bournet, B., … Guillermet-Guibert, J. (2021). Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component. EMBO Molecular Medicine, n/a(n/a), e13502. https://doi.org/10.15252/emmm.202013502 Cite
