Antitumor activity of imatinib mesylate in neuroblastoma xenografts

Received 11 January 2005; accepted 8 February 2005.

Abstract

Imatinib mesylate has antitumor activity in vitro and in vivo against neuroblastoma cell lines and xenografts characterized by a different expression of receptor tyrosine kinases. In this article, we report that imatinib tumor concentration can be independent of the administered dose and does not correlate with the antitumor effect. In xenografts, high-dose administration does not improve imatinib efficacy. In conclusion, there is no clear-cut correlation between the levels of expression for imatinib-responsive targets and the in vitro and in vivo sensitivity. This further suggests that in neuroblastoma the antitumor activity of imatinib may involve the inhibition of other tyrosine kinases and/or pathways.

Keywords: Neuroblastoma, Imatinib mesylate, c-kit, PDGFR α/β, Receptor tyrosine kinases, Xenografts

a Department of Pediatrics, Catholic University, Rome, Italy

b Novartis Institutes for Biomedical Research, Basel, Switzerland

c Department of Pediatrics, La Sapienza University, Viale Regina Elena 324, I-00161 Rome, Italy

d Division of Child Health, School of Reproductive and Developmental Medicine, Liverpool University, Liverpool, UK

e Laboratory of Oncology, Bambino Gesù Children's Hospital, Rome, Italy

Corresponding author. Address: Department of Pediatrics, La Sapienza University, Viale Regina Elena 324, I-00161 Rome, Italy. Tel.: +39 6 4997 9212; fax: +39 6 4997 2580.

PII: S0304-3835(05)00346-0

doi:10.1016/j.canlet.2005.02.054

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