The nuclear factor erythroid-2 related factor 2 (Nrf2) is a pivotal activator of genes encoding cytoprotective and detoxifying enzymes that protect against oxidative and eletrophilic stress. Under normal condition, Nrf2 is localized in the cytoplasm binding to Kelch-like ECH-associated protein 1 (KEAP1), which facilitates the degradation of Nrf2 via the ubiquitin proteasome pathway. Under stress conditions, oxidants or electrophiles abrogate the interaction between KEAP1 with Nrf2, resulting in increased nuclear accumulation of Nrf2 and the transcriptional induction of target genes. Activation of Nrf2 pathway is crucial for cancer chemoprevention. However, over-expression of Nrf2 has been found in many types of cancer, facilitating tumor growth and resistance to anticancer therapy. This article summarises recent progress in understanding the regulation of Nrf2 activity, and the new development in finding small molecules modulating Nrf2/ARE signalling pathway.

Contents
1 Introduction
2 Dual roles of Nrf2 in carcinogenesis
2.1 Activation of Nrf2 is important for cancer chemoprevention
2.2 The dependence of tumour cells on Nrf2
3 The complexity of Nrf2 signaling
3.1 KEAP1-independent Nrf2 degradation
3.2 p21 activates Nrf2 through direct interacting with NRF2
3.3 p62 activates Nrf2 through interacting with KEAP1
3.4 Oncogenes activate Nrf2
3.5 Nuclear receptors inhibit Nrf2 activity
4 Small molecules modulate Nrf2/ARE signalling pathway
4.1 The methods used for identifying novel Nrf2 activators
4.2 The Nrf2 inhibitors
5 Concluding remarks