The quinoxaline anti-tumor agent (R+)XK469 inhibits neuroblastoma tumor growth

• Published in: Pediatric blood & cancer 2011-01, Vol.56 (1), p.164-167
• Main Authors: Kakodkar, Nisha C., Peddinti, Radhika, Kletzel, Morris, Tian, Yufeng, Guerrero, Lisa J., Undevia, Samir D., Geary, David, Chlenski, Alexandre, Yang, Qiwei, Salwen, Helen R., Cohn, Susan L.
• Format: Article
• Language: English
• Subjects: Adolescent; Antineoplastic Agents - pharmacology; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Fatal Outcome; Humans; Neoplasm Metastasis; neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - pathology; phase I; Quinoxalines - pharmacology; Quinoxalines - therapeutic use; relapse; topoisomerase inhibitor; Treatment Outcome; Xenograft Model Antitumor Assays
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.22639

The quinoxaline anti‐tumor agent (R+)XK469 mediates its effects by topoisomerase IIB inhibition. This report describes a 14‐year old with relapsed neuroblastoma who experienced disease stabilization for 14 months while receiving (R+)XK469 monotherapy. Due to this favorable response, laboratory studies were undertaken to determine efficacy in the preclinical setting. (R+)XK469 inhibited proliferation, caused G2 cell cycle arrest of neuroblastoma cells in vitro, and inhibited growth of neuroblastoma xenograft tumors. These preclinical results, coupled with the favorable clinical response, demonstrate that (R+)XK469 and similar anti‐tumor agents may be effective in the treatment of high‐risk neuroblastoma and warrant further testing. Pediatr Blood Cancer. 2010;56:164–167. © 2010 Wiley‐Liss, Inc.