Beyond the membrane: Internalization and compartmentalization of insulin‑like growth factor 1 receptor signaling in cancer pathogenesis and treatment (Review).

The insulin‑like growth factor 1 receptor (IGF‑1R) plays a central role in tumor initiation, progression and response to treatment. IGF‑1R internalization and compartmentalization have profound effects on tumor biology, extending beyond classical signaling associated with receptors at the cell membrane. Following internalization, IGF‑1R alters its intracellular localization and induces new signaling functions. These changes affect the duration and spatial dynamics of signal activation, thereby influencing tumor cell proliferation, migration and the development of drug resistance. However, the exact molecular mechanisms that mediate these processes remain elusive, and the inherent complexity of the downstream signaling network continues to limit the clinical translation of IGF‑1R‑targeted therapies. The present review systematically summarizes the current knowledge on the molecular mechanisms of IGF‑1R internalization and compartmentalization, highlighting their roles in tumor progression and treatment response. The recent advancements and persistent challenges in this field are also critically discussed, aiming to provide a theoretical foundation and new insights for the development of more efficient and effective therapeutic plans that specifically target IGF‑1R.