A newly identified downstream signaling pathway has been described, constituting by tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF) (TRAF2/RAS-NFIA/NFIB-SPDEF), in linking to the aggressive development of lung cancers [151]. The gene discussed is SPDEF; the disease is lung carcinoma.