Although clinical evidence of HGF/MET-targeted drug resistance has not been presented, a preclinical study observed acquired resistance to HGF/MET inhibitors in patients with gastric cancer.346 Under laboratory conditions, suppression of HGF/MET might induce subsequent MET mutations (Y1230 mutation in the MET loop) and compensatory activation of alternative pathways, such as EGFR or the RAS/RAF/MEK pathway, which might inevitably cause secondary resistance to anti-HGF or anti-MET therapies.277. The gene discussed is HGF; the disease is gastric cancer.