What’s New in Thyroid Cancer Research?

Important research into thyroid cancer is being done right now in many university hospitals, medical centers, and other institutions around the country. Each year, scientists find out more about what causes the disease, how to prevent it, and how to improve treatment. In past years, for example, evidence has grown showing the benefits of combining surgery with radioactive iodine therapy and thyroid hormone therapy. The results include higher cure rates, lower recurrence rates, and longer survival.

Genetics

The discovery of the genetic causes of familial (inherited) medullary thyroid cancer now makes it possible to identify family members carrying the abnormal RET gene and to remove the thyroid to prevent cancer from developing there.

Understanding the abnormal genes that cause sporadic (not inherited) thyroid cancer has led to better treatments as well. In fact, treatments that target some of these gene changes are already being used, and more are being developed (see below).

Treatment

Most thyroid cancers can be treated successfully. But advanced cancers can be hard to treat, especially if they do not respond to radioactive iodine (RAI) therapy. Doctors and researchers are looking for new ways to treat thyroid cancer that are more effective and lead to fewer side effects.

Radioactive iodine (RAI) therapy

Doctors are looking for better ways to see which cancers are likely to come back after surgery. Patients with these cancers may be helped by getting RAI therapy after surgery. Recent studies have shown that patients with very low thyroglobulin levels 3 months after surgery have a very low risk of recurrence even without RAI. More research in this area is still needed.

Researchers are also looking for ways to make RAI effective against more thyroid cancers. For example, in some thyroid cancers, the cells have changes in the BRAF gene, which may make them less likely to respond to RAI therapy. Researchers are studying whether new drugs that target the BRAF pathway can be used to make thyroid cancer cells more likely to take up radioactive iodine. These types of drugs might be useful for people who have advanced cancer that is no longer responding to RAI therapy.

Targeted therapies

In general, thyroid cancers do not respond well to chemotherapy. But exciting data are emerging about some newer targeted drugs. Unlike standard chemotherapy drugs, which work by attacking rapidly growing cells (including cancer cells), these drugs attack specific targets on cancer cells. Targeted drugs may work in some cases when standard chemotherapy drugs do not, and they often have different side effects.

Kinase inhibitors: A class of targeted drugs known as kinase inhibitors may help treat thyroid cancer cells with mutations in certain genes, such as BRAF and RET/PTC. Many of these drugs also affect tumor blood vessel growth.

In many papillary thyroid cancers, the cells have changes in the BRAF gene, which helps them grow. Drugs that target cells with BRAF gene changes, such as vemurafenib (Zelboraf), dabrafenib (Tafinlar), and selumetinib, are now being studied in thyroid cancers with this gene change.

In one study, giving selumetinib to patients with thyroid cancers that had stopped responding to radioactive iodine (RAI) treatment helped make some patients’ tumors respond to treatment with RAI again. It helped patients not only with BRAF mutations, but also with mutations in a different gene called NRAS.

Other kinase inhibitors that have shown early promise against thyroid cancer in clinical trials include sunitinib (Sutent), pazopanib (Votrient), and axitinib (Inlyta).

Some of these other drugs, such as sunitinib, sorafenib, and pazopanib, are already approved to treat other types of cancer, and might be useful against MTC and differentiated thyroid cancers if other treatments are no longer working.

Anti-angiogenesis drugs: As tumors grow, they need a larger blood supply to get enough nutrients. They get it by forming new blood vessels (a process called angiogenesis). Anti-angiogenesis drugs work by disrupting these new blood vessels. Some of the drugs listed above, such as axitinib, sunitinib, and sorafenib, have anti-angiogenic properties.

Another anti-angiogenesis drug being studied for use against thyroid cancer is bevacizumab (Avastin).

Other targeted drugs: The combination of the chemotherapy drug paclitaxel (Taxol) with the targeted drug efatutazone could be helpful in patients with anaplastic thyroid cancer. Efatutazone targets a receptor called PPAR-gamma.

Observation

The chance of being diagnosed with thyroid cancer has risen rapidly in the US in recent years. Much of this rise appears to be the result of the increased use of thyroid ultrasound, which can detect small thyroid nodules that might not otherwise have been found in the past.

Recent international studies have suggested that some of these newly found, very small thyroid cancers (known as micro-papillary thyroid cancers) may not need to be treated right away but instead can be safely watched. Ongoing clinical trials in the US are now looking at this same approach.