Dissecting the role of the endogenous antioxidant response in lung cancer
Dr. Volkan Sayin from NYU school of medicine - Perlmutter Cancer Center, USA will give a strategic presentation about "Dissecting the role of the endogenous antioxidant response in lung cancer" during Paris Redox 2017.
Kras-driven non-small cell lung cancer (NSCLC) remains one of the most aggressive and lethal solid tumors. More than 20% of Kras-driven NSCLC acquire mutually exclusive activating mutations in the anti-oxidant transcription factor NRF2 or inactivating mutations in its negative regulator KEAP1. It is well established that loss of NRF2 is detrimental for lung cancers. However, little is known about the functional importance of constitutive activation of NRF2 in tumor progression.
Using a combination of a Kras-driven genetically engineered mouse model and somatic CRISPR/Cas9 genome-engineering approaches we demonstrate the functional importance of NRF2/KEAP1 pathway in lung tumorigenesis. With both metabolomic and focused genetic screening methods we are systematically identifying novel mechanisms underlying the role of Nrf2/Keap1 pathway in lung cancer. We find unique dependencies in Nrf2/Keap1 mutant lung cancer cells which we validate by both genetic and biochmeical approaches. These dependencies highlight therapeutic vulnerabilities in cancer cells with increased anti-oxidant production due to alteration in the Nrf2/Keap1 pathway.
If you are interested to know more about this strategic topic, don't hesitate to participate to Paris Redox 2017.
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