Here, we review potential additional targets and novel therapies of interest in lung adenocarcinoma including targets within the cell surface (receptor tyrosine kinases EGFR, human epidermal growth factor receptor 2, RET, ROS1, mesenchymal–epidermal transition, TRK), targets in intracellular signal transduction (ALK, RAS–RAF–MEK, PI3K–AKT–PTEN, WNT), nuclear targets such as poly-ADP ribose polymerase, heat shock protein 90, and histone deacetylase, and selected pathways in the tumor environment. Here, PIK3CA is linked to lung adenocarcinoma.