 The discovery of EGFR mutations in NSCLC has led to the use of EGFR, TKIs as effective treatments for the disease. Unfortunately, these drugs are not always successful leading to the development of resistance. This resistance can be caused by multiple factors including secondary mutations, activation of alternative pathways, altered signaling pathways, impaired apoptotic pathways, and more. By understanding the mechanisms behind this resistance, researchers hope to identify potential targets for developing new therapeutics. This article was authored by Li Huohuang and Li Wufu.