Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis Oncogenes such as K-Ras, B-Raf, and Myc induce the Nrf2 transcription factor, which enhances ROS detoxification and may promote tumorigenesis. This study shows that oncogenic K-Ras, B-Raf, and Myc increase Nrf2 expression, leading to a more reduced intracellular environment and lower ROS levels. Nrf2 activation is a novel mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-Ras and B-Raf, as well as in human pancreatic cancer. Genetic targeting of the Nrf2 pathway impairs K-Ras-induced proliferation and tumorigenesis in vivo. The Nrf2 antioxidant and cellular detoxification program represents a previously unappreciated mediator of oncogenesis. The study also shows that oncogenic Ras, such as K-Ras, increases Nrf2 expression and activity, which in turn reduces ROS levels and promotes a more reduced intracellular environment. This is in contrast to the ectopic overexpression of oncogenic Ras, which increases ROS production. The study further demonstrates that the activation of Nrf2 by oncogenes is mediated through the Raf-MEK-ERK-Jun pathway. Additionally, the study shows that the Nrf2 antioxidant program is involved in the development of pancreatic cancer, as evidenced by increased Nrf2 expression and reduced ROS levels in pancreatic cancer cells. The study also shows that Nrf2 is involved in the development of lung cancer, as evidenced by reduced disease burden and increased survival in Nrf2-deficient mice. The study concludes that Nrf2 promotes K-Ras-initiated pancreatic and lung tumorigenesis and proliferation. The findings suggest that modulation of the redox state is uniformly important in cancer and may represent a therapeutic opportunity. The study highlights the role of Nrf2 in ROS detoxification and tumorigenesis, and suggests that Nrf2 activation is a key mechanism in oncogenesis.Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis Oncogenes such as K-Ras, B-Raf, and Myc induce the Nrf2 transcription factor, which enhances ROS detoxification and may promote tumorigenesis. This study shows that oncogenic K-Ras, B-Raf, and Myc increase Nrf2 expression, leading to a more reduced intracellular environment and lower ROS levels. Nrf2 activation is a novel mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-Ras and B-Raf, as well as in human pancreatic cancer. Genetic targeting of the Nrf2 pathway impairs K-Ras-induced proliferation and tumorigenesis in vivo. The Nrf2 antioxidant and cellular detoxification program represents a previously unappreciated mediator of oncogenesis. The study also shows that oncogenic Ras, such as K-Ras, increases Nrf2 expression and activity, which in turn reduces ROS levels and promotes a more reduced intracellular environment. This is in contrast to the ectopic overexpression of oncogenic Ras, which increases ROS production. The study further demonstrates that the activation of Nrf2 by oncogenes is mediated through the Raf-MEK-ERK-Jun pathway. Additionally, the study shows that the Nrf2 antioxidant program is involved in the development of pancreatic cancer, as evidenced by increased Nrf2 expression and reduced ROS levels in pancreatic cancer cells. The study also shows that Nrf2 is involved in the development of lung cancer, as evidenced by reduced disease burden and increased survival in Nrf2-deficient mice. The study concludes that Nrf2 promotes K-Ras-initiated pancreatic and lung tumorigenesis and proliferation. The findings suggest that modulation of the redox state is uniformly important in cancer and may represent a therapeutic opportunity. The study highlights the role of Nrf2 in ROS detoxification and tumorigenesis, and suggests that Nrf2 activation is a key mechanism in oncogenesis.