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Genetic dissection of oncogenic Kras signaling in lung cancer

Institution: Stanford University
Investigator(s): Rui Tang, Ph.D.
Award Cycle: 2018 (Cycle 27) Grant #: 27FT-0044 Award: $184,512
Subject Area: Cancer
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. KRAS is one of the most frequently altered genes in human cancer, and mutations in KRAS occur in 30% of lung adenocarcinoma. KRAS is a type of protein called oncogene, which means that when it gets mutated it drives cancer growth. Despite decades of attempts, therapies to directly “turn-off” oncogenic KRAS have not been discovered. There are many different flavors of oncogenic KRAS (called KRAS variants) and oncogenic KRAS controls many different things inside the cancer cell. Personalized medicine directed towards different oncogenic KRAS variants and the things that it controls has great potential for the treatment of KRAS-driven lung cancer.

  My project will answer why and how different KRAS variants causes lung cancer and may uncover novel druggable targets for precision treatment. In my project, I will first study the differences among oncogenic KRAS variants in a lung cancer model. I will also determine which other proteins that touch oncogenic KRAS are actually important for cancer growth. To study different oncogenic KRAS variants in lung cancer, I will replace the normal KRAS gene with different oncogenic Kras variants in the mouse lung. To uncover novel proteins that touch oncogenic Kras, my co-mentor Dr. Peter Jackson's laboratory used a fancy method where they can extract oncogenic Kras from cells and then identify all of the other proteins that are stuck to it. Finally, I will use a powerful system established in our laboratory (which uses CRISPR/Cas9-mediated genome editing) to delete several candidate proteins that bind to Kras and to determine their importance during cancer growth in vivo.

My project is entirely unique from what other people in the field are doing and it has the potential to identify novel therapeutic targets that could aid in the treatment of patients with lung cancer. I hope that my work will make an impact on patients with this devastating disease. I am dedicated to working toward a world in which genetic analysis of lung tumors will enable patients to be treated with the right drugs.