title: The challenge of targeted therapies for gastric cancer patients: the beginning of a long journey.
abstract: BACKGROUND
  Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of patients with advanced disease remains dismal. Collaborative, high-quality research and advances in high-throughput technologies have contributed to elucidate molecular pathways underpinning disease progression and have stimulated many clinical studies testing target therapies in the advanced disease setting. Although progress has been made thanks to trastuzumab in HER2 positive tumours, antiangiogenic drugs have produced conflicting results and EGFR-inhibitors have failed to show major improvements.
  
  
  METHODS
  While commenting on the results of many key Phase III randomized trials, the Authors discuss the most promising classes of novel targeted agents and present the current challenges toward a customized treatment.
  
  
  CONCLUSIONS
  Palliative chemotherapy became the worldwide standard of care for patients with advanced gastric cancers, producing significant life prolongation and improvement of life quality. Nevertheless, long-term outcomes of those patients remain poor. Because of the encouraging advancement in novel targeted therapies, such a disappointing scenario is now evolving. While results serve as a springboard for future research, more comprehensive efforts are needed to clarify the biological mechanisms underpinning cancer progression and help clinicians to develop new effective treatments.
authors.affiliation: University and General Hospital, Department of Medical Oncology , Piazzale S Maria della Misericordia 1, 33100, Udine , Italy +39 432 559308 ; +39 432 559305 ; aprile.giuseppe@aoud.sanita.fvg.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Marta
authors.initials: M
authors.lastname: Bonotto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bittoni
authors.forename: Elena
authors.initials: E
authors.lastname: Ongaro
authors.forename: Giovanni Gerardo
authors.initials: GG
authors.lastname: Cardellino
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D018095:Germ-Line Mutation; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; C066855:HGF protein, human
keywords: MET-inhibitors; gastric cancer; pertuzumab; ramucirumab; target therapy