Developmental targeted therapeutics for brain cancers

We are aware that monotherapy may not work for malignant tumors such as glioblastoma. Search for novel key molecules in these devastating diseases is inevitable. With our patient-derived CSC models and their xenograft models, we have discovered various key molecules and their targeted lead compounds that attenuate various phenotypes in CSCs.

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a. Siomycin A depletes brain tumor stem cells partly through the MELK-mediated pathway. Nakano I (corresponding author), Inagaki A, Watanabe M, Lam D, Leung C, Visnyei K, Okemoto-Nakamura Y, Liang R, Mischel P, and Kornblum HI. Neuro-oncology 2011. 13(6):622-34.
b. Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb. Miyazaki T, Pan Y, Joshi K, Purohit D, Hu B, Demir H, Mazumder S, Okabe S, Yamori T, Viapiano M, Shin-ya K, Seimiya H, and Nakano I. Clin Cancer Res 2012 Mar 1;18(5):1268-80 PMID: 22230766 * Select for the Cover of the issue.
c. Impairment of glioma stem cell survival and growth by a novel inhibitor for Survivin/Ran protein complex. Guvenc H*, Pavlyukov MS*, Kurt H, Joshi K Banasavadi-Siddegowda YK, Mao P, Hong C, Yamada R, Kwon CH, Kitange G, Park IH, Sarkaria JN, Li C, Shakhparonov MI, Nakano I. Clin Cancer Res 2013 Feb 1;19(3):631-42. PMID: 23251006
d. RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model. Lee TJ, Haque F, Shu D, Yoo JY, Li H, Yokel RA, Horbinski C, Kim TH, Kim SH, Kwon CH, Nakano I, Kaur B, Guo P, Croce CM. Oncotarget. 2015 Mar 23
e. Multi-Kinase Inhibitor C1 Triggers Mitotic Catastrophe of Glioma Stem Cells Mainly through MELK Kinase Inhibition. Minata M, Gu C, Joshi K, Nakano-Okuno M, Hong C, Nguyen CH, Kornblum HI, Molla A, Nakano I. PLoS One. 2014 Apr 16;9(4):e92546. doi: 10.1371/journal.pone.0092546. PMID: 24739874