Emerging kinase inhibitors of the treatment of gastric cancer

Introduction: Gastric cancer (GC) is the fifth most common malignancy in theworld. In the last years, for the first time in literature, the addition of atargeted therapy to standard chemotherapy has proved to prolong medianoverall survival. In this scenario, kinase inhibitors (KIs), smaller intracellularagents, could be an interesting and novel type of targeted treatment ofmetastatic GC both in first and further lines of therapy.Areas covered: Several KI have been evaluated in the preclinical setting. Thisreview will underline the most relevant targeted pathways involved in GCtumorigenesis and disease progression including EGFR, VEGFR, c-MET,mTOR, fibroblast growth factor receptor, Src and Aurora kinases.Expert opinion: Despite the good results of TOGA, RAINBOW and REGARDtrials about the addition of monoclonal antibodies to standard of care inGC, the addition of KI seems not to achieve comparable interesting resultsin management of GC. However, an improved patient selection before andduring treatment according to molecular characteristics, as well as combinationstudies evaluating the synergistic effect of combination schedules ofdifferent KIs and standard chemotherapy, or KI plus KI or KI plus antibodiesbasedtherapy may reveal interesting results and lead to understandmechanisms of multi-drug resistance.