Cancer cells must change their metabolism to support the growth and spread of the tumor. Mitochondria, the "power plants of the cell", produce most of the energy used by normal cells. It is becoming clear that most cancers depend on the mitochondria to promote the growth and division of the tumor cells.

The McFadden lab is studying a form of thyroid cancer called Hürthle cell carcinoma in which the mitochondria are defective due to mutations in the DNA within the mitochondria. Hürthle call cancers are a clinical challenge with few treatment options. The McFadden lab has used a laboratory model in which a tumor from a patient with Hurthle carcinoma was grown in mice and then used to...

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Cancer cells must change their metabolism to support the growth and spread of the tumor. Mitochondria, the "power plants of the cell", produce most of the energy used by normal cells. It is becoming clear that most cancers depend on the mitochondria to promote the growth and division of the tumor cells.

The McFadden lab is studying a form of thyroid cancer called Hürthle cell carcinoma in which the mitochondria are defective due to mutations in the DNA within the mitochondria. Hürthle cell cancers are a clinical challenge with few treatment options. The McFadden lab has used a laboratory model in which a tumor from a patient with Hürthle carcinoma was grown in mice and then used to generate Hürthle cells that can be grown in the laboratory. We have shown that the mitochondrial are defective in these cancer cells, but interestingly, Hürthle cancer cells appear to grow just fine without fully functional mitochondria.

The lab has studied metabolism in these cells, and found that Hürthle cancer cells must re-wire metabolism to support growth of the tumor cells. We have identified a specific enzyme that is essential for growth of the cancer cells, and blocking this enzyme leads to death of the cancer cells. In this grant, we propose to determine whether this enzyme is a valid target for treatment in Hürthle cell cancers. We will also enroll thyroid cancer patients into a study that allows us to determine whether defective mitochondria are common in Hürthle cancer and other forms of thyroid cancer. Finally, the lab has developed a method to identify other nutrients that cells with defective mitochondria require for growth in the lab. Together these studies will establish the role of defective mitochondria in Hürthle cell tumors and other forms of thyroid cancer, identify the metabolic adaptations that these cells require to grow in the lab and in tumors, and identify new targets for treatment of these and other forms of cancer that have defective mitochondria.

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