The previous studies in GC suggest that signaling through other receptor tyrosine kinases (RTKs), such as amplification of MET, IGFR, and HER3 confer anti-HER2 treatment resistance by re-stimulating downstream of PI3K and MAPK signal transduction, thus bypassing the inhibitory effect of lapatinib or trastuzumab [37, 38]. The gene discussed is PIK3CA; the disease is gastric cancer.