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“Smart medicines” for advanced thyroid cancers

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Thyroid cells are the only cells in the body that take up and concentrate iodine. Iodine is used to make the thyroid hormones. This feature is used to treat advanced thyroid cancer by using radioactive iodine therapy. The radioactive iodine is taken up by normal and cancerous thyroid cells and destroys them. While most thyroid cancer has an excellent prognosis, some advanced thyroid cancers can be very difficult to treat. A common reason for this is that some advanced cancer cells lose the ability to take up and concentrate the radioactive iodine.

In the past decade, there have been oral “smart medicines” developed aimed at restoring the thyroid cancer cells ability to take up iodine with mixed success. In recent years, physicians have started looking at the genetic make-up of a particular thyroid cancer on a surgical specimen to find a gene mutation that can act as a target for therapy. These genetic mutations might be able to guide physicians as to the specific type of “smart medicine” which will change the non-responsive, very altered thyroid cancer cell closer to its more natural thyroid cell form that did concentrate iodine well. As thyroid cancers respond less and less to radioactive iodine, they get more active and start showing up more and more on PET-CT scans, which measure how active the cells are. This shows that the cancer is getting worse.

The goal of the study is to assess the ability of “smart medicines” known as tyrosine kinase inhibitors to bring thyroid cancer cells closer to their more natural form of the thyroid cell to make radioactive iodine more effective.

Weber M et al 2022 Enhancing radioiodine incorporation into radioiodine-refractory thyroid cancer with MAPK inhibition (ERRITI): A single-center prospective two-arm study. Clin Cancer Res 28:4194–4202. PMID: 35594174.

The study analyzed 20 patients at the University of Duisburg-Essen Hospital in Germany who had structural evidence of thyroid cancer that could not be completely removed or had thyroid cancer that had changed so much that they are no longer responding to radioactive iodine treatments. A PET-CT scan was used both before the treatment with these “smart medicines” and after to assess how much more the thyroid cancer cells were able to take up iodine compared to the original thyroid cell. To qualify for the study, each of the patients’ surgical pathology was evaluated for whether the thyroid cancer contained a mutation of the BRAF V600E gene mutation common in thyroid cancer. Patients with a mutated version were treated with two “smart medicines” dabrafenib and trametinib, while patients without the gene mutation were treated with only dabrafenib for three weeks.

The PET-CT scan performed after 3 weeks of treatment with either the one or two of the “smart medicines” showed that 7 patients’ cancers (35% of the 20 patients studied) were less active and able to respond better to standard radioactive iodine therapy. These cancers were subsequently were treated with high dose (300 mCi) radioactive iodine therapy. After the “smart medicines” treatment and radioactive iodine, 4 out of these 7 patients showed a response with a decrease in blood thyroglobulin levels. The size of the thyroid cancer lesions slightly decreased in 6 out of the 7 patients.

This study shows that in some patients with persistent advanced thyroid cancer that no longer responds to radioactive iodine therapy, treatment with certain novel “smart medicines” can be used to make the cancer more responsive to radioactive iodine therapy. Whether this has any effect on long term prognosis and survival is unclear. However, this provides some hope to thyroid cancer patients for treatment of these advanced thyroid cancers. Over all, this study provides patients and physicians more tools to treat advanced thyroid cancers.

— Pinar Smith, MD


Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass genetic traits to offspring.

Mutation: A permanent change in one of the genes.

BRAF gene: this is gene that codes for a protein that is involved in a signaling pathway and is important for cell growth. Mutations in the BRAF gene in adults appear to cause cancer.

Radioactive iodine (RAI): this plays a valuable role in diagnosing and treating thyroid problems since it is taken up only by the thyroid gland. I-131 is the destructive form used to destroy thyroid tissue in the treatment of thyroid cancer and with an overactive thyroid. I-123 is the nondestructive form that does not damage the thyroid and is used in scans to take pictures of the thyroid (Thyroid Scan) or to take pictures of the whole body to look for thyroid cancer (Whole Body Scan).

Thyroglobulin: a protein made only by thyroid cells, both normal and cancerous. When all normal thyroid tissue is destroyed after radioactive iodine therapy in patients with thyroid cancer, thyroglobulin can be used as a thyroid cancer marker in patients that do not have thyroglobulin antibodies.

Positron-Emission-Tomography (PET-CT) scans: a nuclear medicine imaging test that uses a small amount of radiolabeled glucose to identify cancer. Since cancer cells are more active than normal cells, the cancer cells take up more of the radiolabeled glucose and show up on the PET scan. PET scans are combined with CT scans to accurately identify where the cancer is located.

Iodine: an element found naturally in various foods that is important for making thyroid hormones and for normal thyroid function. Common foods high in iodine include iodized salt, dairy products, seafood and some breads.