Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer

• Published in: Molecules Vol. 26; no. 5; p. 1417
• Main Authors: Telkoparan-Akillilar, Pelin, Panieri, Emiliano, Cevik, Dilek, Suzen, Sibel, Saso, Luciano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.03.2021; MDPI
• Subjects: Animals; Antioxidants; Cancer; Cell division; Epigenesis, Genetic; Gene expression; Genes, Tumor Suppressor; Homeostasis; Humans; Keap1; Kelch-Like ECH-Associated Protein 1 - genetics; Kelch-Like ECH-Associated Protein 1 - metabolism; Kinases; Metastasis; Molecular Targeted Therapy - methods; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; NF-E2-Related Factor 2 - antagonists & inhibitors; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress; Proteins; Review; Roles; Signal Transduction; Transcription factors; Tumorigenesis; Tumors; Keap1; cancer; Nrf2; oxidative stress
• ISSN: 1420-3049; 1433-1373; 1420-3049; 1433-1373
• DOI: 10.3390/molecules26051417

Cancer is one of the most fatal diseases with an increasing incidence and mortality all over the world. Thus, there is an urgent need for novel therapies targeting major cancer-related pathways. Nuclear factor-erythroid 2-related factor 2 (NRF2) and its major negative modulator Kelch-like ECH-associated protein 1 (KEAP1) are main players of the cellular defense mechanisms against internal and external cell stressors. However, NRF2/KEAP1 signaling pathway is dysregulated in various cancers, thus promoting tumor cell survival and metastasis. In the present review, we discuss the mechanisms of normal and deregulated NRF2 signaling pathway focusing on its cancer-related functions. We further explore activators and inhibitors of this pathway as cancer targeting drug candidates in order to provide an extensive background on the subject.