The Keap1-Nrf2 Signaling Pathway in Lung Cancer

The survival and proliferation of lung cancers widely depend on various signaling pathways; Keap1-Nrf2-ARE is one of the primary pathways in lung cancers. The principal function of Nrf2 is to offer protection to cells from stress induced by xenobiotics through the activation of cytoprotective transcriptional programs. Nrf2 is a Janus-faced transcription factor that can act both as a preneoplastic or an antineoplastic in cancers. In lung cancers, persistent activation of Nrf2 offers resistance to chemotherapeutic drugs and radiotherapy thereby facilitates proliferation. The sustainable Nrf2 actuation impacts the different hallmarks of cancers such as proliferation, metastasis, angiogenesis, and apoptosis. In aberrantly activated Nrf2 lung cancers, inhibitors of Nrf2 can act as therapeutic agents. In this chapter, we highlight the relationship between lung cancers and Keap1-Nrf2- ARE signaling with an emphasis on the dysregulation of Keap1-Nrf2 signaling, Keap1 and Nrf2 mutations, microRNAs in Keap1-Nrf2 signaling, smoking and Nrf2 activation in lung cancer, and Keap1-Nrf2 pathway as a therapeutic target.