The role of FGFR signaling in SCLC and NSCLC: Current insights and therapeutic perspectives
TL;DR
It is proposed that FGFR signaling functions as a context-dependent adaptive node, whose therapeutic significance emerges under selective pressure and acquired resistance, which reflects constraints of alteration-centered targeting rather than an absence of biological relevance.
Abstract
Summary Lung cancer remains a leading cause of cancer related mortality worldwide and is characterized by marked biological heterogeneity and frequent therapeutic failure. Although lung cancer is broadly classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on distinct cellular origins and clinical behaviors, both entities rely on aberrant signaling networks to sustain tumor growth and disease progression. Despite advances in biomarker guided therapeutic strategies, approaches centered on individual genetic alterations have shown limited durability, in part due to tumor evolution and cellular plasticity. Among signaling pathways shared across lung cancer subtypes, fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFR) signaling has been implicated in regulating tumor proliferation, angiogenesis, and adaptive responses to therapy. Here, we argue that the limited clinical success of FGFR-targeted therapies in lung cancer reflects constraints of alteration-centered targeting rather than an absence of biological relevance. We propose that FGFR signaling functions as a context-dependent adaptive node, whose therapeutic significance emerges under selective pressure and acquired resistance.