KIF11 inhibitors filanesib and ispinesib inhibit meningioma growth in vitro and in vivo.
Treatment of aggressive meningiomas remains challenging due to a high rate of recurrence in higher-grade meningiomas, frequent subtotal resections, and the lack of effective systemic treatments. Substantial overexpression associated with a poor prognosis has been demonstrated for kinesin family member 11 (KIF11) in high-grade meningiomas. Due to anti-tumor activity for KIF11 inhibitors (KIF11i) filanesib and ispinesib in other cancer types, we sought to investigate their mode of action and efficacy for the treatment of aggressive meningiomas. Dose curve analysis of both KIF11i revealed IC50 values of less than 1 nM in anaplastic and benign meningioma cell lines. Both compounds induced G2/M arrest and subsequent subG1 increase in all cell lines. Profound induction of apoptosis was detected in the anaplastic cell lines determined by annexin V staining. KIF11i significantly inhibited meningioma growth in xenotransplanted mice by up to 83%. Furthermore, both drugs induced minor hematological side effects, which were less pronounced for filanesib. We identified substantial in vitro and in vivo anti-tumor effects of the KIF11 inhibitors filanesib and ispinesib, with filanesib demonstrating better tolerability, suggesting future use of filanesib for the treatment of aggressive meningioma.
['Jungwirth|Gerhard|G|', 'Yu|Tao|T|', 'Cao|Junguo|J|', 'Eddine|Montadar Alaa|MA|', 'Moustafa|Mahmoud|M|', 'Warta|Rolf|R|', 'Debus|Juergen|J|', 'Unterberg|Andreas|A|', 'Abdollahi|Amir|A|', 'Herold-Mende|Christel|C|']
D000818:Animals D001549:Benzamides D045744:Cell Line, Tumor D049109:Cell Proliferation D005260:Female D059565:G2 Phase Cell Cycle Checkpoints D006801:Humans D016547:Kinesins D008577:Meningeal Neoplasms D008579:Meningioma D051379:Mice D011799:Quinazolines D013830:Thiadiazoles D023041:Xenograft Model Antitumor Assays
KIF11 Filanesib Ispinesib Meningioma NCH93