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.