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Mutant K-Ras-Mediated Oxidative Stress in Pancreatic Cancer

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Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly lethal cancers with dismal prognosis due to lack of effective targeted therapies and resistance to chemotherapeutic drugs. Significant genetic alterations have been identified as the foremost cause for the instigation and propagation of PDAC, among which K-ras mutations are known as the driver mutation. Oncogenic expression of mutated K-ras results in metabolic changes and altered intracellular signaling pathways that can upsurge the level of cellular reactive oxygen species (ROS). Increase in ROS production further drives the progression of pre-cancerous intraepithelial lesions (PanIN) in pancreas. In order to keep ROS at a level where they are pro-tumorigenic and proliferative but not toxic, antioxidant defense systems are also upregulated in mutant K-ras driven neoplasia. This chapter brings a broad view on mutant K-ras mediated generation of ROS and the mechanisms of overcoming the deleterious effects of ROS through ROS detoxification systems during PDAC tumorigenesis.

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Authors and Affiliations

  1. Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    Divya Thomas, Satish Sagar & Prakash Radhakrishnan

  2. Iowa State University, Iowa, USA

    Tristan Caffrey

  3. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    Prakash Radhakrishnan

  4. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    Prakash Radhakrishnan

  5. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA

    Prakash Radhakrishnan

Authors
  1. Divya Thomas
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  2. Satish Sagar
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  3. Tristan Caffrey
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  4. Prakash Radhakrishnan
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Correspondence to Prakash Radhakrishnan .

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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA

    Bimal K. Ray

  3. CSIR-Indian Institute of Chemical Biology, Kolkata, India

    Susanta Roychoudhury

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Thomas, D., Sagar, S., Caffrey, T., Radhakrishnan, P. (2022). Mutant K-Ras-Mediated Oxidative Stress in Pancreatic Cancer. In: Chakraborti, S., Ray, B.K., Roychoudhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-9411-3_94

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