Translational Cancer Research on RTK Signaling

At Lauriola Lab, we investigate how tyrosine kinase membrane receptors (RTKs) orchestrate tissue homeostasis through transcriptional feedback loops, and how their dysregulation fuels colorectal cancer progression and resistance to therapy. Our research reveals that resistance to EGFR-targeting monoclonal antibodies such as cetuximab (CTX) is not solely driven by genetic alterations, but also by non-mutational mechanisms, notably inflammatory signaling. In non-responder patients, we have identified a post-senescent phenotype marked by IL-1 production, sustaining a drug-tolerant, pro-tumor microenvironment—findings that highlight the potential of combining EGFR and IL-1 inhibition as a promising strategy for metastatic colorectal cancer. Beyond EGFR, we uncovered the ALK–ALKAL2 autocrine loop as a novel, actionable vulnerability in Consensus Molecular Subtype 1 (CMS1) colorectal cancer, where wild-type ALK drives proliferation, survival, and migration, and whose inhibition may offer a targeted therapeutic opportunity. We are also advancing studies on the MET receptor, exploring its role in shaping peri-nuclear actin structures, nuclear architecture, cell signaling, and genomic stability during migration, with the goal of unveiling new therapeutic approaches to limit DNA damage, tumor plasticity, and metastatic spread.