In the last years, several efforts have been made to classify colorectal cancer (CRC) into well-defined molecular subgroups, representing the intrinsic inter-patient heterogeneity, known as Consensus Molecular Subtypes (CMSs). In this work, we performed a meta-analysis of 1700 CRC patients stratified into four CMSs. We identified a negative correlation between a high level of anaplastic lymphoma kinase (ALK) expression and relapse-free survival, exclusively in CMS1 subtype. Stemming from this observation, we tested several CMSs in vitro models with crizotinib (CZB) or alectinib (ALC), potent ALK inhibitors, already approved for clinical use. ALK interception strongly inhibits cell proliferation already at nanomolar doses, specifically in CMS1 cell lines, while no effect was found in CMS2/3/4 groups. Furthermore, in vivo imaging identified a role for ALK in the dynamic formation of 3D spheroids, which was impaired by the pharmacological inhibition of ALK. Consistently, CZB was responsib..... READ ARTICLE
BioRxiv DOI:10.1101/2020.10.07.307991
Authors: Martina Mazzeschi, Michela Sgarzi, Donatella Romaniello, Valerio Gelfo, Carola Cavallo, Spartaco Santi, Michelangelo Fiorentino, Gabriele D’Uva, Balázs Győrffy, Ruth Palmer, Mattia Lauriola
