Alberto J Arribas, Sara Napoli, Luciano Cascione, Laura Barnabei, Giulio Sartori, Eleonora Cannas, Eugenio Gaudio, Chiara Tarantelli, Afua A Mensah, Filippo Spriano, Antonella Zucchetto, Francesca M Rossi, Andrea Rinaldi, Manuel Castro de Moura, Sandra Jovic, Roberta Bordone Pittau, Anastasios Stathis, Georg Stussi, Valter Gattei, Jennifer R Brown, Manel Esteller, Emanuele Zucca, Davide Rossi, Francesco Bertoni
BTK and PI3K inhibitors are among the drugs approved for the treatment of patients with lymphoid neoplasms. Although active, their ability to lead to long-lasting complete remission is rather limited, especially in the lymphoma setting. This indicates that tumor cells often develop resistance to the drugs. We started from a marginal zone lymphoma cell line, Karpas-1718, kept under prolonged exposure to the PI3Kδ inhibitor idelalisib until acquisition of resistance, or with no drug. Cells underwent transcriptome, miRNA and methylation profiling, whole-exome sequencing, and pharmacologic screening, which led to the identification of the overexpression of ERBB4 and its ligands HBEGF and NRG2 in the resistant cells...
December 5, 2023: Molecular Cancer Therapeutics