title: Sapacitabine  for cancer.
abstract: BACKGROUND
  Sapacitabine is an orally bioavailable nucleoside analog prodrug that is in clinical trials for hematologic malignancies and solid tumors. The active metabolite of sapacitabine, CNDAC (2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine), exhibits the unique mechanism of action of causing single-strand breaks (SSBs) after incorporation into DNA, which are converted into double-strand breaks (DSBs) when cells enter a second S-phase. CNDAC-induced DSBs are predominantly repaired through homologous recombination (HR). Cells deficient in HR components are greatly sensitized to CNDAC. Therefore, sapacitabine could be specifically effective against tumors that are deficient in this repair pathway.
  
  
  METHODS
  This review summarizes results from supporting evidence for the mechanisms of action of sapacitabine, its preclinical activities and the current results of clinical trials in a variety of cancers. The novel action mechanism of sapacitabine is discussed, with a view to validate it as a chemotherapeutic drug targeting malignancies with defects in HR.
  
  
  CONCLUSIONS
  Knowledge of CNDAC mechanism identifies tumors that may be sensitized to sapacitabine, thus enabling a personalized treatment strategy. It also creates the opportunity to overcome resistance to current front-line therapies and identify synergistic interactions with known anticancer drugs. The results of such investigations may provide rationales for the design of sapacitabine-based clinical trials.
authors.affiliation: The University of Texas M.D. Anderson Cancer Center, Department of Experimental Therapeutics, Houston, TX, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: William
authors.initials: W
authors.lastname: Plunkett
mesh_terms: D000818:Animals; D001087:Arabinonucleosides / Q000494:pharmacology* / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002986:Clinical Trials as Topic; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004249:DNA Damage; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D001087:Arabinonucleosides; D011355:Prodrugs; D003596:Cytosine; C117959:sapacitabine