Adrián Álvarez-Varela, Laura Novellasdemunt, Francisco M Barriga, Xavier Hernando-Momblona, Adrià Cañellas-Socias, Sara Cano-Crespo, Marta Sevillano, Carme Cortina, Diana Stork, Clara Morral, Gemma Turon, Felipe Slebe, Laura Jiménez-Gracia, Ginevra Caratù, Peter Jung, Giorgio Stassi, Holger Heyn, Daniele V F Tauriello, Lidia Mateo, Sabine Tejpar, Elena Sancho, Camille Stephan-Otto Attolini, Eduard Batlle
Colorectal cancer (CRC) patient-derived organoids predict responses to chemotherapy. Here we used them to investigate relapse after treatment. Patient-derived organoids expand from highly proliferative LGR5+ tumor cells; however, we discovered that lack of optimal growth conditions specifies a latent LGR5+ cell state. This cell population expressed the gene MEX3A, is chemoresistant and regenerated the organoid culture after treatment. In CRC mouse models, Mex3a+ cells contributed marginally to metastatic outgrowth; however, after chemotherapy, Mex3a+ cells produced large cell clones that regenerated the disease...
September 2022: Nature Cancer