Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program

• Published in: Pediatric blood & cancer 2013-08, Vol.60 (8), p.1325-1332
• Main Authors: Kolb, E. Anders, Gorlick, Richard, Reynolds, C. Patrick, Kang, Min H., Carol, Hernan, Lock, Richard, Keir, Stephen T., Maris, John M., Billups, Catherine A., DesJardins, Christopher, Kurmasheva, Raushan T., Houghton, Peter J., Smith, Malcolm A.
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; developmental therapeutics; Furans - pharmacology; Hematology; Humans; Ketones - pharmacology; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - pathology; Oncology; Pediatrics; PI3K inhibitor; preclinical testing; Tubulin Modulators - pharmacology; Xenograft Model Antitumor Assays - methods
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.24517

Background Antimitotic agents are essential components for curative therapy of pediatric acute leukemias and many solid tumors. Eribulin is a novel agent that differs from both Vinca alkaloids and taxanes in its mode of binding to tubulin polymers. Procedures Eribulin was tested against the PPTP in vitro cell line panel at concentrations from 0.1 nM to 1.0 μM and against the PPTP in vivo xenograft panels at a dose of 1 mg/kg (solid tumors) or 1.5 mg/kg (ALL models) using a q4dx3 schedule repeated at Day 21. Results In vitro eribulin demonstrated cytotoxic activity, with a median relative IC50 value of 0.27 nM, (range