 The incidence of non-small cell lung cancer, NSCLC, has increased significantly in recent years, making it one of the leading causes of death worldwide. The majority of these cases are caused by mutated epidermal growth factor receptors, EGFRs, which can be targeted with EGFR tyrosine kinase inhibitor, TKI, treatments. Unfortunately, many patients develop resistance to this type of treatment, resulting in poor outcomes. In order to combat this problem, researchers have been investigating various mechanisms of resistance, such as the activation of alternative signaling pathways, the development of secondary mutations, and the alteration of downstream pathways. Additionally, the development of new generation drugs is necessary to overcome resistance to current EGFR TKs. This article was authored by Carmela Laface, Felicia Maria Macelli, Anna Nataligia Centoro, and others.