CRM1 as a potential biomarker and therapeutic target in cancer: a comprehensive review

Abdul Razak AR, Mau-Soerensen M, Gabrail NY, Gerecitano JF, Shields AF, Unger TJ, et al. First-in-class, first-in-human phase I study of selinexor, a selective inhibitor of nuclear export, in patients with advanced solid tumors. J Clin Oncol. 2016;34(34):4142–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Abeykoon JP, Hampel PJ, King RL, Wood AJ, Larson MC, Nowakowski KE, et al. The significance of gradient expression of chromosome region maintenance protein 1 (exportin1) in large cell lymphoma. Haematologica. 2021;106(8):2261–4.

Article  PubMed  PubMed Central  Google Scholar 

Alexander TB, Lacayo NJ, Choi JK, Ribeiro RC, Pui C-H, Rubnitz JE. Phase I study of selinexor, a selective inhibitor of nuclear export, in combination with fludarabine and cytarabine, in pediatric relapsed or refractory acute leukemia. J Clin Oncol. 2016;34(34):4094–101.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Argueta C, Kashyap T, Klebanov B, Unger TJ, Guo C, Harrington S, et al. Selinexor synergizes with dexamethasone to repress mTORC1 signaling and induce multiple myeloma cell death. Oncotarget. 2018;9(39):25529–44.

Article  PubMed  PubMed Central  Google Scholar 

Aumann WK, Kazi R, Harrington AM, Wechsler DS. Novel—and not so novel—inhibitors of the multifunctional CRM1 protein. Oncol Rev. 2024;18:1427497.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Azmi AS, Aboukameel A, Bao B, Sarkar FH, Philip PA, Kauffman M, et al. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology. 2013;144(2):447–56.

Article  CAS  PubMed  Google Scholar 

Baek HB, Lombard AP, Libertini SJ, Fernandez-Rubio A, Vinall R, Gandour-Edwards R, et al. XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies. Oncotarget. 2018;9(77):34567–81.

Article  PubMed  PubMed Central  Google Scholar 

Bai B, Moore HM, Laiho M. CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis. Nucleus. 2013;4(4):315–25.

Article  PubMed  PubMed Central  Google Scholar 

Baumhardt JM, Walker JS, Lee Y, Shakya B, Brautigam CA, Lapalombella R, et al. Recognition of nuclear export signals by CRM1 carrying the oncogenic E571K mutation. Mol Biol Cell. 2020;31(17):1879–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berezikov E, Guryev V, Plasterk RHA, Cuppen E. CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting. Genome Res. 2004;14(1):170–8.

Article  CAS  PubMed  Google Scholar 

Bonazzi S, Eidam O, Güttinger S, Wach J-Y, Zemp I, Kutay U, et al. Anguinomycins and derivatives: total syntheses, modeling, and biological evaluation of the inhibition of nucleocytoplasmic transport. J Am Chem Soc. 2010;132(4):1432–42.

Article  CAS  PubMed  Google Scholar 

Cai X, Liu X. Inhibition of Thr-55 phosphorylation restores p53 nuclear localization and sensitizes cancer cells to DNA damage. Proc Natl Acad Sci. 2008;105(44):16958–63.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen Y, Camacho SC, Silvers TR, Razak ARA, Gabrail NY, Gerecitano JF, et al. Inhibition of the nuclear export receptor XPO1 as a therapeutic target for platinum-resistant ovarian cancer. Clin Cancer Res. 2017;23(6):1552–63.

Article  CAS  PubMed  Google Scholar 

Chook YM, Jung A, Rosen MK, Blobel G. Uncoupling Kapβ2 substrate dissociation and ran binding. Biochemistry. 2002;41(22):6955–66.

Article  CAS  PubMed  Google Scholar 

Crochiere M, Kashyap T, Kalid O, Shechter S, Klebanov B, Senapedis W, et al. Deciphering mechanisms of drug sensitivity and resistance to Selective Inhibitor of Nuclear Export (SINE) compounds. BMC Cancer. 2015;15(1):910.

Article  PubMed  PubMed Central  Google Scholar 

Cromie MM, Gao W. Epigallocatechin-3-Gallate enhances the therapeutic effects of Leptomycin B on human lung cancer A549 cells. Oxid Med Cell Longev. 2015;2015:1–10.

Article  Google Scholar 

Dong X, Biswas A, Chook YM. Structural basis for assembly and disassembly of the CRM1 nuclear export complex. Nat Struct Mol Biol. 2009;16(5):558–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, et al. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 2003;17(10):1253–70.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Etchin J, Sanda T, Mansour MR, Kentsis A, Montero J, Le BT, et al. KPT -330 inhibitor of CRM 1 ( XPO 1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T -cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Br J Haematol. 2013;161(1):117–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farren MR, Hennessey RC, Shakya R, Elnaggar O, Young G, Kendra K, et al. The Exportin-1 inhibitor selinexor exerts superior antitumor activity when combined with T-cell checkpoint inhibitors. Mol Cancer Ther. 2017;16(3):417–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferreira BI, Cautain B, Grenho I, Link W. Small molecule inhibitors of CRM1. Front Pharmacol. 2020;11:625.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fiedler W, Heuser M, Chromik J, Thol F, Bokemeyer C, Theile S, et al. Phase II results of Ara-C and Idarubicin in combination with the selective inhibitor of nuclear export (SINE) compound selinexor (KPT-330) in patients with relapsed or refractory AML. Blood. 2016;128(22):341–341.

Article  Google Scholar 

Fisher JG, Bartlett LG, Kashyap T, Walker CJ, Khakoo SI, Blunt MD. Modulation of anti-tumour immunity by XPO1 inhibitors. Explor Target Anti-Tumor Ther. 2025;6:1002310.

Article  CAS  Google Scholar 

Freedman DA, Levine AJ. Nuclear export is required for degradation of endogenous p53 by MDM2 and Human Papillomavirus E6. Mol Cell Biol. 1998;18(12):7288–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gadal O, Strauß D, Kessl J, Trumpower B, Tollervey D, Hurt E. Nuclear export of 60S ribosomal subunits depends on Xpo1p and requires a nuclear export sequence-containing factor, Nmd3p, that associates with the large subunit protein Rpl10p. Mol Cell Biol. 2001;21(10):3405–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gao W, Lu C, Chen L, Keohavong P. Overexpression of CRM1: a characteristic feature in a transformed phenotype of lung carcinogenesis and a molecular target for lung cancer adjuvant therapy. J Thorac Oncol. 2015;10(5):815–25.

Article  CAS  PubMed  Google Scholar 

García-Santisteban I, Arregi I, Alonso-Mariño M, Urbaneja MA, Garcia-Vallejo JJ, Bañuelos S, et al. A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K. Cell Mol Life Sci CMLS. 2016;73(24):4685–99.

Article  PubMed  PubMed Central  Google Scholar 

Hecht SS. Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol. 2002;3(8):461–9.

Article  CAS  PubMed  Google Scholar 

Hecht SS. Tobacco smoke carcinogens and lung cancer. JNCI J Natl Cancer Inst. 1999;91(14):1194–210.

Article  CAS  PubMed 

Comments (0)

No login
gif