title: Durable complete response of metastatic gastric cancer with anti-Met therapy followed by resistance at recurrence.
abstract: A 48 year-old female with chemo-refractory metastatic gastric cancer to the liver was treated on a Phase I clinical trial with MetMAb, a monoclonal antibody targeting the Met tyrosine kinase receptor. The primary tumor had high MET gene polysomy and evidence for an autocrine production of HGF, the growth factor ligand of Met. A complete response was obtained lasting two years; the cancer recurred as a peritoneal deposit invading into the transverse colon and a gastrohepatic ligament node. Compassionate use of MetMAb therapy at recurrence achieved a mixed response--a partial response of the two initial lesions, but with development of multiple new foci of carcinomatosis. Tissue and serum studies evaluating the Met signaling pathway did correlate with MetMAb treatment response initially and at the time of recurrence.
  
  
  CONCLUSIONS
  This research brief is the first to describe a durable complete response obtained with a molecularly targeted monoclonal antibody, MetMAb, to the receptor tyrosine kinase, Met, in a patient with chemorefractory metastatic gastric cancer. It is also the first to report biomarkers that predicted therapeutic response to Met inhibition.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA. dcatenac@medicine.bsd.uchicago.edu
authors.forename: Daniel V T
authors.initials: DV
authors.lastname: Catenacci
authors.forename: Les
authors.initials: L
authors.lastname: Henderson
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Xiao
authors.forename: Premal
authors.initials: P
authors.lastname: Patel
authors.forename: Robert L
authors.initials: RL
authors.lastname: Yauch
authors.forename: Priti
authors.initials: P
authors.lastname: Hegde
authors.forename: Jiping
authors.initials: J
authors.lastname: Zha
authors.forename: Ajay
authors.initials: A
authors.lastname: Pandita
authors.forename: Amy
authors.initials: A
authors.lastname: Peterson
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004351:Drug Resistance; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000628:therapy*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met