Lung cancer is the leading cause of cancer-associated death, with many people succumbing to the disease within a year of diagnosis. This highlights the urgent need to find new ways to target and treat lung cancer. Our laboratory studies an important metabolic enzyme called NADK2, which is frequently found to be amplified in lung cancer. However, we still don't fully understand why lung cancer cells have more NADK2 or what role it plays in their growth. We made an interesting discovery that when we delete NADK2 from lung cancer cells, they become unable to produce a specific building block called proline, which they need to grow. Cells in our bodies can make proline on their own, so they do...

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Lung cancer is the leading cause of cancer-associated death, with many people succumbing to the disease within a year of diagnosis. This highlights the urgent need to find new ways to target and treat lung cancer. Our laboratory studies an important metabolic enzyme called NADK2, which is frequently found to be amplified in lung cancer. However, we still don't fully understand why lung cancer cells have more NADK2 or what role it plays in their growth. We made an interesting discovery that when we delete NADK2 from lung cancer cells, they become unable to produce a specific building block called proline, which they need to grow. Cells in our bodies can make proline on their own, so they do not need to rely on proline from our diet to function. This opens up the possibility of using proline-free diets to stop the growth of lung cancer cells when combined with NADK2-blocking treatments. Additionally, we found that lung cancer cells without NADK2 become more sensitive to drugs that inhibit their energy production. This means that we could potentially use drugs that target energy production along with blocking NADK2 activity to effectively kill lung cancer cells. Here, we propose to advance our understanding of the metabolic functions of NADK2 that benefit lung cancer cells during tumor growth and exploit these metabolic mechanisms to develop therapies for lung cancer. Using a genetic mouse model that mimics lung cancer in humans, we propose two strategies to attack lung cancer cells: (1) NADK2 deletion with/without a proline-free diet; and (2) NADK2 deletion with/without a drug that inhibits energy production. Overall, our work will determine if targeting NADK2 can be an effective way to treat lung cancer and if combining it with a proline-free diet or energy-blocking drugs can eradicate lung tumor cells.

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