Otol Neurotol. 2008 Sep;29(6):846-53.
ErbB inhibitors trastuzumab and erlotinib inhibit growth of vestibular
schwannoma xenografts in nude mice: a preliminary study.
Clark JJ, Provenzano M, Diggelmann HR, Xu N, Hansen SS, Hansen MR.
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242-1078, USA.
To analyze the ability of ErbB inhibitors to reduce the growth of
vestibular schwannoma (VS) xenografts.
METHODS: Vestibular schwannoma
xenografts were established in the interscapular fat pad in nude mice
for 4 weeks. Initially, a small cohort of animals was treated with the
ErbB2 inhibitor trastuzumab or saline for 2 weeks. Animals also
received bromodeoxyuridine injections to label proliferating cells. In
a longer-term experiment, animals were randomized to receive
trastuzumab, erlotinib (an ErbB kinase inhibitor), or placebo for 12
weeks. Tumor growth was monitored by magnetic resonance imaging during
the treatment period. Cell death was analyzed by terminal
deoxynucleotidyl transferase-mediated dUTP-biotin end labeling of
RESULTS: Tumors can be distinguished with T2-weighted
magnetic resonance imaging sequences. Trastuzumab significantly reduced
the proliferation of VS cells compared with control (p < 0.01) as
analyzed by bromodeoxyuridine uptake. Control tumors demonstrated
slight growth during the 12-week treatment period. Both trastuzumab and
erlotinib significantly reduced the growth of VS xenografts (p <
0.05). Erlotinib, but not trastuzumab, resulted in a significant
increase in the percentage of terminal deoxynucleotidyl
transferase-mediated dUTP-biotin end labeling of fragmented
DNA-positive VS cells (p < 0.01).
CONCLUSION: In this preliminary
study, the ErbB inhibitors trastuzumab and erlotinib decreased growth
of VS xenografts in nude mice, raising the possibility of using ErbB
inhibitors in the management of patients with schwannomas, particularly
those with neurofibromatosis Type 2.