title: Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges.
abstract: OBJECTIVE
  5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.
  
  
  METHODS
  All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or "hepatocellular carcinoma" or "pancreatic adenocarcinoma" or "esophageal cancer" or "gallbladder carcinoma" or "gastric cancer").
  
  
  METHODS
  Critical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy.
  
  
  RESULTS
  Most cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.
  
  
  CONCLUSIONS
  Autophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.
authors.forename: Jia-Cheng
authors.initials: JC
authors.lastname: Tang
authors.forename: Yi-Li
authors.initials: YL
authors.lastname: Feng
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of General Surgery, Zhejiang Province Key Laboratory of Laparosopic Technology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, China.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Cai
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001343:Autophagy / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil