Targeting melanoma with NT157 by blocking Stat3 and IGF1R signaling

Oncogene. 2016 May 19;35(20):2675-80. doi: 10.1038/onc.2015.229. Epub 2015 Jun 29.

Abstract

It is well known that specific signal transduction inhibitors rarely suffice as anti-cancer agents. In most cases, tumors possess primary drug resistance due to their inherent heterogeneity, or acquire drug resistance due to genomic instability and acquisition of mutations. Here we expand our previous study of the novel compound, NT157, and show that it acts as a dual-targeting agent that invokes the blockage of two signal transduction pathways that are central to the development and maintenance of multiple human cancers. We show that NT157 targets not only IGF1R-IRS1/2, as previously reported, but also the Stat3 signaling pathway and demonstrates remarkable anti-cancer characteristics in A375 human melanoma cells and in a metastatic melanoma model in mice.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Drug Discovery
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Molecular Targeted Therapy / methods*
  • Neoplasm Invasiveness
  • Pyrogallol / analogs & derivatives*
  • Pyrogallol / pharmacology
  • Pyrogallol / therapeutic use
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*
  • Sulfonamides / pharmacology*
  • Sulfonamides / therapeutic use

Substances

  • Antineoplastic Agents
  • IGF1R protein, human
  • NT157 compound
  • Receptors, Somatomedin
  • STAT3 Transcription Factor
  • Sulfonamides
  • Pyrogallol
  • Receptor, IGF Type 1