The poor prognosis for patients with esophagogastric cancers (EGC) has resulted 
in an increased focus on the use of targeted agents in this disease. Targets 
include epidermal growth factor receptor (EGFR), vascular endothelial growth 
factor (VEGF), Her2, mammalian target of rapamycin (mTOR), MET, poly 
(ADP-ribose) polymerase (PARP) and claudin 18.2 (CLDN18.2). Trastuzumab, an 
anti-Her2 antibody, was approved by the U.S. FDA in 2010 as first-line therapy 
in combination with chemotherapy for Her2-positive disease. Since then, 
strategies targeting Her2 that have been successful in Her2-positive breast 
cancer, have failed in EGC. The one remaining study, the phase III Jacob study 
with pertuzumab, has yet to be presented. The anti-VEGF receptor 2 antibody, 
ramucirumab has been investigated as second-line therapy in 2 phase III trials, 
which resulted in improved survival, with subsequent FDA approval of ramucirumab 
in the second-line setting. Therapies targeting EGFR have been evaluated in a 
number of phase III studies, all of which have been negative. Phase III 
investigation of an mTOR inhibitor did not improve survival, although biomarker 
studies are awaited which may identify subgroups of patients that may benefit 
from its use. The results of the trials targeting MET in EGC have been 
disappointing, raising doubts about the usefulness of further testing agents 
that inhibit the MET pathway. PARP inhibition with olaparib, warrants further 
investigation, possibly in combination with other targeted therapies or immune 
checkpoint inhibition and in a biomarker-selected population. The identification 
of CLDN18.2 and its targeting with claudiximab is very promising and will be 
further investigated in a phase III study.