TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000264031
  • Gene Name:UPK2
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:HTI-286
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:prostate cancer
  • Tissue:cell lines (PC-3)

Other information

  • Title:Targeting prostate cancer with HTI-286, a synthetic analog of the marine sponge product hemiasterlin
  • Journal:Int J Cancer
  • Published:2008
  • PubMed ID:18240145
  • Abstract:Therapeutic resistance is the underlying cause for most cancer deaths and a major problem associated with treatment of metastatic prostate cancer. HTI-286, a fully synthetic analog of the natural tripeptide hemiasterlin, inhibits tubulin polymerization and circumvents transport-based resistance to taxanes. In our study, we evaluated its inhibitory effects on human prostate cancer growth in vitro and in different in vivo models. Androgen-dependent and androgen-independent prostate cancer cell lines including a docetaxel-refractory PC-3 subline (PC-3dR) were treated with HTI-286. Transcriptional profiling was carried out to screen for changes in gene expression induced by HTI-286 and compared to docetaxel. In vivo, nude mice with established PC-3 or PC-3dR xenografts were given HTI-286 intravenously. Additionally, mice bearing hormone-sensitive LNCaP tumors were treated with castration in combination with early or delayed HTI-286 therapy. In all cell lines tested, HTI-286 was a potent inhibitor of proliferation and induced marked increases in apoptosis. Despite similar transcriptomic changes regarding cell death and cell cycle regulating genes after exposure to HTI-286 or docetaxel, array analysis revealed distinct molecular signatures for both compounds. Invivo, HTI-286 significantly inhibited growth of PC-3 and LNCaP xenografts and retained potency in PC-3dR tumors. Simultaneous castration plus HTI-286 therapy was superior to sequential treatment in the LNCaP model. In conclusion, HTI-286 showed strong antitumor activity both in androgen-dependent and androgen- independent tumors and may be a promising agent in second- line treatment strategies for patients suffering from docetaxel- refractory prostate cancer.
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