PIK3CD and gastric cancer: Our study has validated the approach and revealed the potential molecular mechanisms for the treatment of subsets of GC cases: loss-of-function mutation of CSK or PTEN causes resistance to lapatinib in HER2-amplified GC cells via hyperactivation of PI3K and MAPK pathways, which can be overcome by applying drug combination of lapatinib, PI3K and MAPK pathway inhibitors.