title: In Vitro and In Vivo Studies of a New Class of Anticancer Molecules for Targeted Radiotherapy of Cancer.
abstract: There is a compelling need to develop anticancer therapies that target cancer cells and tissues. Arising from innovative femtomedicine studies, a new class of non-platinum-based halogenated molecules (called FMD molecules) that selectively kill cancer cells and protect normal cells in treatments of multiple cancers has been discovered. This article reports the first observation of the radiosensitizing effects of such compounds in combination with ionizing radiation for targeted radiotherapy of a variety of cancers. We present in vitro and in vivo studies focused on combination with radiotherapy of cervical, ovarian, head and neck, and lung cancers. Our results demonstrate that treatments of various cancer cells in vitro and in vivo mouse xenograft models with such compounds led to enhanced efficiencies in radiotherapy, while the compounds themselves induced no or little radiotoxicity toward normal cells or tissues. These compounds are therefore effective radiosensitizers that can be translated into clinical trials for targeted radiotherapy of multiple types of cancer. This study also shows the potential of femtomedicine to bring breakthroughs in understanding fundamental biologic processes and to accelerate the discovery of novel drugs for effective treatment or prevention of a variety of cancers. Mol Cancer Ther; 15(4); 640-50. ©2016 AACR.
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Wang
authors.affiliation: Princess Margaret Cancer Centre and Ontario Cancer and Techna Institutes, University Health Network, Toronto, Ontario, Canada. Department of Radiation Oncology, School of Medicine, University of Maryland, Baltimore, Maryland.
authors.forename: Javed
authors.initials: J
authors.lastname: Mahmood
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Qin-Rong
authors.initials: QR
authors.lastname: Zhang
authors.affiliation: Princess Margaret Cancer Centre and Ontario Cancer and Techna Institutes, University Health Network, Toronto, Ontario, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Vedadi
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Warrington
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Ning
authors.initials: N
authors.lastname: Ou
authors.affiliation: Princess Margaret Cancer Centre and Ontario Cancer and Techna Institutes, University Health Network, Toronto, Ontario, Canada. Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. qblu@uwaterloo.ca david.jaffray@rmp.uhn.on.ca Rob.Bristow@rmp.uhn.on.ca.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.affiliation: Princess Margaret Cancer Centre and Ontario Cancer and Techna Institutes, University Health Network, Toronto, Ontario, Canada. Departments of Radiation Oncology and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. qblu@uwaterloo.ca david.jaffray@rmp.uhn.on.ca Rob.Bristow@rmp.uhn.on.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Jaffray
authors.affiliation: Department of Physics and Astronomy, University of Waterloo, Waterloo, Ontario, Canada. Departments of Biology and Chemistry, University of Waterloo, Waterloo, Ontario, Canada. qblu@uwaterloo.ca david.jaffray@rmp.uhn.on.ca Rob.Bristow@rmp.uhn.on.ca.
authors.forename: Qing-Bin
authors.initials: QB
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D055808:Drug Discovery; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011878:Radiotherapy; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents