Enhancing immunotherapy efficacy in colorectal cancer: targeting the FGR-AKT-SP1-DKK1 axis with DCC-2036 (Rebastinib).

ABSTRACT: This research demonstrates that DCC-2036 (Rebastinib), a potent third-generation tyrosine kinase inhibitor (TKI), effectively suppresses tumor growth in colorectal cancer (CRC) models with functional immune systems. The findings underscore the capacity of DCC-2036 to enhance both the activation and cytotoxic functionality of CD8⁺ T cells, which are crucial for facilitating anti-tumor immune responses. Through comprehensive multi-omics investigations, significant shifts in both gene and protein expression profiles were detected, notably a marked decrease in DKK1 levels. This reduction in DKK1 was linked to diminished CD8⁺ T cell effectiveness, correlating with decreased FGR expression. Moreover, our findings identify FGR as a pivotal modulator that influences DKK1 expr

SUBMITTER: Chen X 

PROVIDER: S-EPMC11718245 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature