title: 5-Fluorouracil derivatives: a patent review (2012 - 2014).
abstract: BACKGROUND
  5-Fluorouracil (5-FU)-based chemotherapy is the most widely prescribed treatment for gastrointestinal solid tumors, but there are several drawbacks such as toxicities, lack of selectivity and effectiveness as well as the development of resistance that need to be overcome.
  
  
  METHODS
  In this review, the authors present the latest innovations in 5-FU derivatives or combinations with: i) other chemotherapeutic drugs; ii) novel targeted compounds; iii) radiotherapy; iv) mAbs; v) siRNA strategies; and vi) traditional Chinese medicine extracts. Moreover, advances to overcome or determine 5-FU adverse effects and effectiveness are described. Finally, the authors introduce the ongoing clinical trials and highlight the main challenges to be addressed in the future.
  
  
  CONCLUSIONS
  Although in the past few years there has been a great advancement in the antitumor effectiveness and selectivity of 5-FU-based therapies, it is envisaged that future approaches using 'omics' technologies that could determine the tumor heterogeneity may help in identifying additional candidate genes, microRNAs or cytokines involved in both the path mechanisms of 5-FU-related toxicity and its therapeutic efficacy. Moreover, the development of novel targeted 5-FU derivatives or 5-FU-based therapies tailored to individual patients opens up new possibilities in the improvement of the quality of life and survival for those suffering from this devastating disease.
authors.affiliation: a 1 University of Granada, Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research , Granada E-18100, Spain +34 958 249 321 ; +34 958 246 296 ; jmarchal@ugr.es.|b 2 University of Granada, Faculty of Medicine, Department of Human Anatomy and Embryology , Granada E-18012, Spain.|c 3 University Hospitals of Granada-Univesity of Granada, Biosanitary Institute of Granada (ibs.GRANADA) , Granada, Spain.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Carrillo
authors.affiliation: d 4 University of Granada, Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research , Granada E-18100, Spain.
authors.forename: Saúl Abenhamar
authors.initials: SA
authors.lastname: Navarro
authors.affiliation: e 5 University of Jaén, Department of Health Sciences , Jaén E-23071, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ramírez
authors.affiliation: f 6 University Hospitals of Granada-Univesity of Granada, Biosanitary Institute of Granada (ibs.GRANADA), Department of Oncology , Granada, Spain.
authors.forename: María Ángel
authors.initials: MÁ
authors.lastname: García
authors.affiliation: a 1 University of Granada, Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research , Granada E-18100, Spain +34 958 249 321 ; +34 958 246 296 ; jmarchal@ugr.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Griñán-Lisón
authors.affiliation: e 5 University of Jaén, Department of Health Sciences , Jaén E-23071, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Perán
authors.affiliation: a 1 University of Granada, Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research , Granada E-18100, Spain +34 958 249 321 ; +34 958 246 296 ; jmarchal@ugr.es.|b 2 University of Granada, Faculty of Medicine, Department of Human Anatomy and Embryology , Granada E-18012, Spain.|c 3 University Hospitals of Granada-Univesity of Granada, Biosanitary Institute of Granada (ibs.GRANADA) , Granada, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Marchal
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D010330:Patents as Topic; D011788:Quality of Life
chemical_list: D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D035683:MicroRNAs; D005472:Fluorouracil
keywords: 5-fluoro-2′-deoxyuridine; 5-fluorouracil; aflibercept; capecitabine; cholestanol; deuteration; leucovorin; mAbs; microRNA; siRNA