Suppression of malignant rhabdoid tumors through Chb-M'-mediated RUNX1 inhibition.

Affiliation

Daifu T(1), Mikami M(1), Hiramatsu H(1), Iwai A(1), Umeda K(1), Noura M(2), Kubota H(1), Masuda T(2), Furuichi K(2), Takasaki S(2), Noguchi Y(2), Morita K(2), Bando T(3), Hirata M(4), Kataoka TR(4), Nakahata T(5), Kuwahara Y(6), Iehara T(7), Hosoi H(7), Takita J(1), Sugiyama H(3), Adachi S(1)(2), Kamikubo Y(2).
Author information:
(1)Department of Pediatrics, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
(2)Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
(3)Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, Japan.
(4)Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
(5)Drug Discovery Technology Development Office, Center for iPS Cell Research and Application
(CiRA), Kyoto University, Sakyo-ku, Kyoto, Japan.
(6)Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
(7)Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.

Abstract

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive pediatric malignancy primarily affecting infants and young children. Intensive multimodal therapies currently given to MRT patients are not sufficiently potent to control this highly malignant tumor. Therefore, additive or alternative therapy for these patients with a poor prognosis is necessary. We herein demonstrated that the inhibition of runt-related transcription factor 1 (RUNX1) by novel alkylating conjugated pyrrole-imidazole (PI) polyamides, which specifically recognize and bind to RUNX-binding DNA sequences, was highly effective in the treatment of rhabdoid tumor cell lines in vitro as well as in an in vivo mouse model. Therefore, suppression of RUNX1 activity may be a novel strategy for MRT therapy.