The autocrine loop of ALK receptor and ALKAL2 ligand is an actionable target in consensus molecular subtype 1 colon cancer.

ABSTRACT:

Background

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).

Methods

In this work, we performed a meta-analysis of 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 cell lines, patient-derived organoids and mice with potent ALK inhibitors, already approved for clinical use.

Results

ALK interception strongly inhibits cell proliferation already at nanomolar doses, specifically in CMS1 cell lines, while no e

SUBMITTER: Mazzeschi M 

PROVIDER: S-EPMC8962179 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature