title: Emerging kinase inhibitors of the treatment of gastric cancer.
abstract: BACKGROUND
  Gastric cancer (GC) is the fifth most common malignancy in the world. In the last years, for the first time in literature, the addition of a targeted therapy to standard chemotherapy has proved to prolong median overall survival. In this scenario, kinase inhibitors (KIs), smaller intracellular agents, could be an interesting and novel type of targeted treatment of metastatic GC both in first and further lines of therapy.
  
  
  METHODS
  Several KI have been evaluated in the preclinical setting. This review will underline the most relevant targeted pathways involved in GC tumorigenesis and disease progression including EGFR, VEGFR, c-MET, mTOR, fibroblast growth factor receptor, Src and Aurora kinases.
  
  
  CONCLUSIONS
  Despite the good results of TOGA, RAINBOW and REGARD trials about the addition of monoclonal antibodies to standard of care in GC, the addition of KI seems not to achieve comparable interesting results in management of GC. However, an improved patient selection before and during treatment according to molecular characteristics, as well as combination studies evaluating the synergistic effect of combination schedules of different KIs and standard chemotherapy, or KI plus KI or KI plus antibodies-based therapy may reveal interesting results and lead to understand mechanisms of multi-drug resistance.
authors.affiliation: a University Campus Biomedico - Medical Oncology , Via Alvaro del Portillo, 200, Rome 00128, Italy b.vincenzi@unicampus.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Marco
authors.initials: M
authors.lastname: Imperatori
authors.forename: Marianna
authors.initials: M
authors.lastname: Silletta
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marrucci
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases
keywords: EGFR; HER2; MET; VEGFR; aurora kinase A; cyclin-dependent kinase; gastric cancer; kinase inhibitors; targeted therapy