Igf1r, the insulin-like growth factor 1 receptor, is a cell-surface, tyrosine-kinase-containing heterotetramer. It mediates the biological activities of insulin-like growth factors (IGFs), which are crucial for different cellular and organism functions. The IGF1R is linked to numerous cytoplasmic signaling cascades such as the PI3K-AKT pathway, and plays a key role in malignant transformation, cell survival, and growth [1].

In pancreatic β-cells, mouse models with decreased IGF1/IGF1R signaling, like Ames Dwarf mice (lacking growth hormone and having reduced IGF1 levels) and inducible β-cell-specific IGF1R knockdown (βIgf1rKD) mice, showed suppressed senescence, improved glucose clearance, and enhanced insulin-secretory function. Deletion of Igf1R in mouse β-cells also led to the restoration of certain signaling pathways and regulation of genes related to β-cell identity and senescence [2]. In non-small cell lung cancer (NSCLC), circ_PPAPDC1A promotes Osimertinib resistance by sponging miR-30a-3p to activate the Igf1r/PI3K/AKT/mTOR pathway [3].

In conclusion, Igf1r is essential for mediating IGF-related cellular functions. Studies using gene-knockdown mouse models have revealed its role in pancreatic β-cell function and senescence, as well as in NSCLC drug resistance. These findings contribute to understanding diseases related to cellular senescence and cancer drug resistance, potentially providing new therapeutic targets.