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  • Nilotinib and lapatinib are effective for treatment of NF2 related schwannomas in the mouse xenograft model

    Final Number:
    503

    Authors:
    Iddo Paldor MD; Nicolas Bonne; Antonella Mangraviti; Jaishri Blakeley MD; Yuan Wang; marco Giovannini; Henry Brem MD; Betty Tyler BA

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2014 Annual Meeting

    Introduction: As advances have been made in our understanding of the pathophysiology of schwanommas related to neurofibromatosis type 2 (NF2), therapeutics that target signaling pathways, angiogenesis, and DNA repair mechanisms are being investigated. Lapatinib, a small tyrosine kinase inhibitor of EGFR/Erb2, Bevacizumab,an anti-VEGF monoclonal antibody, Nilotinib, a multi-target kinase inhibitor, and Everolimus, an inhibitor of mTOR were evaluated the efficacy in a xenograft model of NF2-related peripheral schwanomma.

    Methods: 40 athymic mice were injected with the human cell line SC4 in the anterior flank. When the tumors were measurable(6 days after injection) the mice were randomly divided into 5 groups. Control received no treatment; everolimus, nilotinib, and lapatinib were given orally, daily; and bevacizumab was given intravenously 2x/week. Tumor measurements were performed by manual caliper on alternate days and tumor volume was calculated.

    Results: Average tumor volumes at baseline were 60.51±2.71mm3. Tumor volumes were matched between groups. After 14 days of treatment the experiment ended and animals sacrificed. The average tumor size after two weeks of treatment was 45.6mm3 in the lapatinib group, 57.8mm3 in the nilotinib group, 147.3mm3 in the avastin group, 157.8mm3 in the everolimus group and 227mm3 in the control group.

    Conclusions: Nilotinib and lapatinib both seem to have a positive effect in this model of NF2 related peripheral schwanomma. Bevacizumab and everolimus have beneficiary effects, yet to a lesser degree than the kinase inhibitors. Further research is required to evaluate whether this effect is additive to radiation treatment, and whether it can be shown in a controlled environment in vitro.

    Patient Care: Nilotinib and lapatinib, as well as other kinase inhibitors, should be further explored clinically.

    Learning Objectives: Participants should understand that nilotinib and lapatinib have a positive effect in an NF2 related peripheral schwanomma and that bevacizumab and everolimus have beneficiary effects as well but to a lesser degree than the kinase inhibitors.

    References:

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