Clinical outcome in children with recurrent neuroblastoma treated with ABT-751 and effect of ABT-751 on proliferation of neuroblastoma cell lines and on tubulin polymerization in vitro

Pediatr Blood Cancer. 2010 Jan;54(1):47-54. doi: 10.1002/pbc.22267.


Background: ABT-751, an orally bioavailable sulfonamide, binds beta-tubulin to inhibit microtubule polymerization. We described response and event-free survival (EFS) in children with neuroblastoma and other solid tumors receiving ABT-751, assessed in vitro cytotoxicity of ABT-751 and evaluated the effect of ABT-751 on tubulin polymerization in peripheral blood mononuclear cells (PBMC) and pediatric tumor cell lines.

Procedure: Patients with neuroblastoma (n = 50) or other solid tumors (n = 26) enrolled on the ABT-751 pediatric phase I and pilot trials were reviewed. The sulforhodamine B (SRB) and ACEA Real-Time Cell Electronic Sensing (RT-CES) assays were used to determine the in vitro cytotoxicity. Pharmacodynamic effects on tubulin polymerization/depolymerization were assessed by Western blot and confocal microscopy using antibodies specific for post-translational modifications of polymerized tubulin.

Results: Forty-five patients with neuroblastoma were evaluated for anti-tumor response. No complete or partial responses were documented. The median EFS was 9.3 weeks for children with neuroblastoma and 3.3 weeks for children other solid tumors (P < 0.0001). The ABT-751 IC(50) was 0.6-2.6 mcM in neuroblastoma and 0.7-4.6 mcM in other solid tumor cell lines. Following drug exposure, polymerized tubulin decreased in a concentration- and time-dependent manner in cell lines.

Conclusions: In children treated with ABT-751, the EFS is longer in children with neuroblastoma as compared to other diagnoses. In vitro, ABT-751 was cytotoxic at concentrations tolerable in children. Effects of ABT-751 on polymerization and microtubule structure were time- and dose-dependent but not dependent on tumor type.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Pilot Projects
  • Prognosis
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Survival Rate
  • Treatment Outcome
  • Tubulin / metabolism*
  • Tubulin Modulators / pharmacology
  • Tubulin Modulators / therapeutic use*


  • ABT751
  • Sulfonamides
  • Tubulin
  • Tubulin Modulators