Tyrosine kinase inhibitor therapy of TKI-sensitive lung cancers inactivates HER3 signalling and downstream PI3K/Akt signalling, but HER3 signalling in TKI-resistant lung cancers appears to be uncoupled from EGFR and resistant to inactivation by TKIs (Engelman et al, 2005). The gene discussed is EGFR; the disease is lung carcinoma.