Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.

Academic Article

Abstract

  • Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies, such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side-effect profile. In this study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo We successfully demonstrated decreased cellular proliferation, invasion and migration, cell-cycle arrest, and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should be further investigated as a developing therapeutic in these rare and difficult-to-treat pediatric solid organ tumors. Mol Cancer Ther; 15(5); 911-21. ©2016 AACR.
  • Published In

    Keywords

  • Animals, Antineoplastic Agents, Apoptosis, Cell Cycle Checkpoints, Cell Line, Tumor, Cell Movement, Cell Survival, Disease Models, Animal, Drug Evaluation, Preclinical, Fatty Acids, Unsaturated, Humans, Kidney Neoplasms, Liver Neoplasms, Mice, Mice, Nude, Naphthalenes, Retinoid X Receptors, Tumor Burden, Xenograft Model Antitumor Assays
  • Digital Object Identifier (doi)

    Pubmed Id

  • 16362841
  • Author List

  • Waters AM; Stewart JE; Atigadda VR; Mroczek-Musulman E; Muccio DD; Grubbs CJ; Beierle EA
  • Start Page

  • 911
  • End Page

  • 921
  • Volume

  • 15
  • Issue

  • 5