title: Targeting telomerase with radiolabeled inhibitors.
abstract: The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells,123I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An123I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC50of 1.58 μM (MST-312 IC50: 0.23 μM). Clonogenic assays showed a dose dependant effect of123I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435.
authors.affiliation: CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK. Electronic address: pawaghorn@gmail.com.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Waghorn
authors.affiliation: CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK. Electronic address: mark.jackson.2@glasgow.ac.uk.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Jackson
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. Electronic address: veronique.gouverneur@chem.ox.ac.uk.
authors.forename: Veronique
authors.initials: V
authors.lastname: Gouverneur
authors.affiliation: CR-UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK. Electronic address: katherine.vallis@oncology.ox.ac.uk.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Vallis
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007456:Iodine Isotopes / Q000494:pharmacology / Q000627:therapeutic use; D011836:Radiation Tolerance / Q000187:drug effects*; D011868:Radioisotopes / Q000494:pharmacology / Q000627:therapeutic use; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D007456:Iodine Isotopes; C470197:MST 312; D011868:Radioisotopes; D019098:Telomerase
keywords: Iodine-123; Targeted radionuclide therapy; Telomerase; Telomerase inhibitors