title: A novel cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to gemcitabine.
abstract: 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.
authors.affiliation: Rexahn Pharmaceuticals, Rockville, MD, U.S.A.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Yang
authors.affiliation: Rexahn Pharmaceuticals, Rockville, MD, U.S.A.
authors.forename: Young Bok
authors.initials: YB
authors.lastname: Lee
authors.affiliation: Rexahn Pharmaceuticals, Rockville, MD, U.S.A.
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Ahn
authors.affiliation: Teva Pharmaceuticals Industries LTD., Petach Tikva, Israel.
authors.forename: Joel
authors.initials: J
authors.lastname: Kaye
authors.affiliation: Teva Pharmaceuticals Industries LTD., Petach Tikva, Israel.
authors.forename: Tania
authors.initials: T
authors.lastname: Fine
authors.affiliation: Teva Pharmaceuticals Industries LTD., Petach Tikva, Israel.
authors.forename: Rina
authors.initials: R
authors.lastname: Kashi
authors.affiliation: Teva Pharmaceuticals Industries LTD., Petach Tikva, Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Ohne
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Smid
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.affiliation: Rexahn Pharmaceuticals, Rockville, MD, U.S.A. kimdj@rexahn.com.
authors.forename: Deog Joong
authors.initials: DJ
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003562:Cytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; C000589325:fluorocyclopentenylcytosine; D003562:Cytidine; D000093542:Gemcitabine
keywords: RX-3117; cancer; cytidine analog; drug resistance; gemcitabine