title: Combining anti-tumor alkyl-phospholipid analogs and radiotherapy: rationale and clinical outlook.
abstract: Our improved understanding of the molecular processes that determine cellular sensitivity to ionizing radiation has accelerated the identification of new targets for intervention. Indeed, novel agents have become available for combined clinical use to overcome radioresistance and increase the therapeutic ratio of radiotherapy. Synthetic alkyl-phospholipid analogs (APLs), such as edelfosine, ilmofosine, miltefosine, perifosine and erucylphosphocholine, are a novel class of anti-tumor agents that target cell membranes to induce growth arrest and apoptosis. In addition, APLs strongly enhance the cytotoxic effect of radiation in preclinical models making these compounds attractive candidates as clinical radiosensitizers. In this review, we will discuss mechanisms of action underlying the rationale to combine APLs with radiotherapy and highlight the clinical perspective of this novel combined modality treatment.
authors.forename: Marcel
authors.initials: M
authors.lastname: Verheij
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Moolenaar
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. m.verheij@nki.nl.
authors.forename: Wim J van
authors.initials: WJ
authors.lastname: Blitterswijk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D010743:Phospholipids; D011838:Radiation-Sensitizing Agents