Preclinical evaluation of lestaurtinib (CEP-701) in combination with retinoids for neuroblastoma.

ABSTRACT:

Purpose

Lestaurtinib (CEP-701), a multi-kinase inhibitor with potent activity against the Trk family of receptor tyrosine kinases, has undergone early phase clinical evaluation in children with relapsed neuroblastoma. We studied the interaction of CEP-701 with isotretinoin (13cRA) and fenretinide (4HPR), two retinoids that have been studied in children with high-risk neuroblastoma.

Methods

In vitro growth inhibition was assessed following a 72-hour drug exposure using the sulforhodamine B (SRB) assay in eight neuroblastoma cell lines with variable TrkB expression. When appropriate, the combination index (CI) of Chou-Talalay was used to characterize the interaction of 13cRA (non-constant ratio) or 4HPR (constant ratio) with CEP-701.

Results

The median (range) IC(50) of

SUBMITTER: Norris RE 

PROVIDER: S-EPMC4135359 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature