A novel cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to gemcitabine

Anticancer Res. 2014 Dec;34(12):6951-9.


RX-3117 (fluorocyclopentenylcytosine) is a cytidine analog and this class of drugs, including gemcitabine, has been widely used for the treatment of various types of cancers. However, there is no oral formulation of gemcitabine and drug resistance to gemcitabine is common. In this study, the efficacy of orally-administered RX-3117 was examined in 9 different human tumor xenograft models (colon, non-small cell lung, small cell lung, pancreatic, renal and cervical), grown subcutaneously in athymic nude mice. In the Colo 205, H460, H69 and CaSki models, gemcitabine treatment resulted in 28%, 30%, 25% and 0% tumor growth inhibition (TGI), respectively, whereas oral treatment with RX-3117 induced 100%, 78%, 62% and 66% TGI, respectively. This indicates that RX-3117 may have the potential to be used for the treatment of tumors that do not respond to gemcitabine. RX-3117 was also evaluated in a single primary low-passage human pancreatic Tumorgraft™CTG-0298 (TGI 76%), which is relatively resistant to gemcitabine (TGI 38%) and has a favorable RX-3117-activating enzyme profile. These studies demonstrated the therapeutic potential and anticancer efficacy of RX-3117.

Keywords: RX-3117; cancer; cytidine analog; drug resistance; gemcitabine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Cell Line, Tumor
  • Cytidine / administration & dosage
  • Cytidine / analogs & derivatives*
  • Cytidine / therapeutic use
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease Models, Animal
  • Drug Resistance, Neoplasm*
  • Female
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Xenograft Model Antitumor Assays


  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • fluorocyclopentenylcytosine
  • Cytidine
  • gemcitabine