XPO1 (exportin-1)

Notes

original target text: XPO1 (exportin-1) inhibitor

XPO1, also called exportin-1, is a transport protein that shuttles hundreds of other proteins and some RNA species from the cell nucleus to the cytoplasm. Among its cargo are several tumor suppressor proteins and growth-regulatory factors, including p53, FOXO family transcription factors, and the inhibitor protein IκB. In many cancers, XPO1 is overexpressed, and this drives excessive export of these regulatory proteins out of the nucleus, effectively silencing their protective functions and allowing unchecked cell survival and proliferation signaling to continue. Inhibiting XPO1 blocks this nuclear export machinery, causing tumor suppressor proteins to accumulate within the nucleus, where they can resume their normal roles in halting cell division and promoting programmed cell death in malignant cells. This mechanism is broadly relevant across hematologic malignancies and certain solid tumors, particularly in settings where standard therapies have lost effectiveness, because it acts on a fundamental trafficking process rather than a single mutated oncogene. Because the nuclear export pathway is shared by both cancerous and healthy cells, the approach carries a narrow window between therapeutic effect and toxicity to normal tissue, a balance that continues to shape how such agents are developed and dosed.