title: Nucleoside analogs: ready to enter the era of precision medicine?
abstract: BACKGROUND
  The term 'precision medicine' has garnered significant attention in the oncological setting in relation to attempts to optimize anticancer treatment. Precision medicine is mostly associated with oral targeted therapies and biotherapies, however, to date classic cytotoxics still remain the backbone of most regimens for treating solid tumors or in hematology, both in children and in adults. Among the existing cytotoxic therapies, nucleosides are widely used for treating a variety of cancerous diseases, alone or as part of combination therapies.
  
  
  METHODS
  Several markers at the tumor or the germinal levels have been identified as being associated with clinical outcome (e.g. CDA, DPD, EONFS1, hENT1, TYMS, MTHFR), however little effort has been made to implement bioguided therapy with nucleoside analogs. Still, growing clinical evidence has demonstrated how the efficacy-toxicity balance of these drugs could be improved by developing bioguided strategies at the bedside. This review covers the current knowledge regarding putative markers to be used with nucleoside analogs, what is known on their pharmacokinetic/pharmacodynamic relationships, and provides clues for implementing precision medicine with those old, yet pivotal drugs.
  
  
  CONCLUSIONS
  Through a variety of strategies ranging from pharmacogenetics, tumor genomics and pharmacokinetically-driven adaptive dosing procedures, nucleoside analogs could enter the era of precision medicine in oncology.
authors.affiliation: a SMARTc Unit , Inserm S_911 CRO2 Aix-Marseille University , Marseille , France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ciccolini
authors.affiliation: b Assistance Publique Hôpitaux de Marseille. Multidisciplinary Oncology & Therapeutic Innovations dpt , Aix Marseille University , Marseille , France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Serdjebi
authors.affiliation: a SMARTc Unit , Inserm S_911 CRO2 Aix-Marseille University , Marseille , France.
authors.forename: Hau
authors.initials: H
authors.lastname: Le Thi Thu
authors.affiliation: a SMARTc Unit , Inserm S_911 CRO2 Aix-Marseille University , Marseille , France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
authors.affiliation: c Oncopharmacology Unit , Centre Antoine Lacassagne , Nice , France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Milano
authors.affiliation: a SMARTc Unit , Inserm S_911 CRO2 Aix-Marseille University , Marseille , France.
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Fanciullino
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009705:Nucleosides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000379:methods; D057285:Precision Medicine / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009705:Nucleosides
keywords: Nucleoside analogues; adaptive dosing; pharmacogenetics; pharmacokinetics; therapeutic drug monitoring