This site is intended for US healthcare professionals only.

    Overexpression of XPO1, a nuclear export protein, is one of the mechanisms of oncogenesis1-4

    Labelled image of XPO1 in a healthy cell
    Labelled image of XPO1 in a healthy cell
    For illustrative purposes only.

    In healthy cells:

    • XPO1 is a nuclear export protein1,2,5
    • It is responsible for carrying cargos out of the nucleus1,2
      • Cargos include*:
        Tumor suppressor proteins: p53, p73, FOXO3a, IκB, pRb, BRCA12,6
        Growth regulators: glucocorticoid receptors7
        Oncoprotein mRNA: c-Myc, cyclin D, Bcl‑2, Bcl‑63,6,8,9
    • The process is highly regulated to maintain the appropriate balance of cell growth and apoptosis3,10
    *The identified cargos do not represent all cargos exported by XPO1.2

    XPOVIO® (selinexor) is the first and only FDA-approved oral XPO1 inhibitor that selectively binds to and blocks XPO15

    Annotated diagram showing some cancer cells not exposed to XPOVIO®
    Annotated diagram showing some cancer cells not exposed to XPOVIO®

    Some cancer cells not exposed to XPOVIO

    • XPO1 is overexpressed1-4
    • The nuclear export of cargos into the cytoplasm is increased3,6,9
    • With these important cargos mislocalized, the cancer cell is free to grow and survive2,3,10
    Annotated diagram showing some cancer cells exposed to XPOVIO® (selinexor)
    Annotated diagram showing some cancer cells exposed to XPOVIO® (selinexor)

    Some cancer cells exposed to XPOVIO5

    • XPOVIO blocks XPO1 so it can’t carry cargos out of the nucleus
    • The cargos accumulate in the nucleus
    • This accumulation causes cell cycle arrest and apoptosis
    For illustrative purposes only.
    In nonclinical studies, selinexor demonstrated pro-apoptotic activity in vitro
    in multiple myeloma cells and patient tumor samples, and in murine xenograft models5

    References: 1. Yang J, Bill MA, Young GS, et al. Novel small molecule XPO1/CRM1 inhibitors induce nuclear accumulation of TP53, phosphorylated MAPK and apoptosis in human melanoma cells. PLoS One. 2014;9(7):e102983. 2. Gupta A, Saltarski JM, White MA, Scaglioni PP, Gerber DE. Therapeutic targeting of nuclear export inhibition in lung cancer. J Thorac Oncol. 2017;12(9):1446-1450. 3. Sun Q, Chen X, Zhou Q, Burstein E, Yang S, Jia D. Inhibiting cancer cell hallmark features through nuclear export inhibition. Signal Transduct Target Ther. 2016;1:16010. 4. Mor A, White MA, Fontoura BM. Nuclear trafficking in health and disease. Curr Opin Cell Biol. 2014;28:28-35. 5. XPOVIO (selinexor) [package insert]. Newton, MA: Karyopharm Therapeutics Inc.; July 2019. 6. Gravina GL, Senapedis W, McCauley D, Baloglu E, Shacham S, Festuccia C. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol. 2014;7:85. 7. Vandevyver S, Dejager L, Libert C. On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic. 2012;13(3):364-374. 8. Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ. 2006;13(8):1351-1359. 9. Gandhi UH, Senapedis W, Baloglu E, et al. Clinical implications of targeting XPO1-mediated nuclear export in multiple myeloma. Clin Lymphoma Myeloma Leuk. 2018;18(5):335-345. 10. Tai YT, Landesman Y, Acharya C, et al. CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications. Leukemia. 2014;28(1):155-165.