Thyroid Cancer Outfoxed

A molecule called FOXO3a was thought to be a keen cancer fighter. Instead, when it comes to thyroid cancer, it's actually a fox in the hen house.

FOXO3a does not suppress cancer. Instead, it supports the growth of cancer - it's a lethal cancer promoter.

A study at Mayo Clinic revealed how the molecule has outfoxed cancer researchers.

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When FOXO3a was silenced in a model of human anaplastic thyroid cancer, scientists found that thyroid cancer cell growth slowed instead of speeding up. Scientists thought that without the protection of FOXO3a, cancer growth would explode.

"This result is exactly the opposite of what we expected," senior author John A. Copland, PhD, a Mayo cancer biologist, said. "We were more than surprised. We were concerned."

FOXO3a has been known to suppress tumor growth because it deals with the stress cells undergo, including cancer processes.

In the study, researchers used a drug to block Akt, a molecule that keeps cancer cells alive. Scientists thought that this would increase FOXO3a, which would then turn off the growth of anaplastic thyroid cancer, a rare but deadly cancer.

"We discovered a biological switch that turns FOXO3a from a good guy into a bad actor, but we don't know what that is yet, or in which cancers that might happen," said lead researcher Laura Marlow, a Mayo biologist.

Dr. Copland wants to spread the word on this and warn other researchers, including those testing Akt inhibitors (blockers).

"Cancer researchers, including those testing Akt inhibitors, should know that FOXO3a has pro-cancer activity as well as anti-cancer properties," Dr. Copland says. "Concern should be raised that an Akt inhibitor will enhance retention of FOXO3a in the nucleus, causing FOXO3a to remain active."

The study also had a bright side. A gene - cyclin A1 - was found to be involved in cancer cell growth and may become a druggable target.

This research was published in the June issue of Journal of Cell Science.

The study was funded the National Institutes of Health/National Cancer Institute, Mayo Clinic Research Committee; Florida Department of Health Bankhead-Coley Cancer Research Program; a gift from Alfred D. and Audrey M. Petersen; a grant for rare cancers from Dr. Ellis and Dona Brunton, and TGEN Institutional Research Funds.

Potential conflicts of interest were not publicly available.
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Thyroid Cancer

The American Cancer Society estimates that there are over 48,000 new cases of thyroid cancer each year in the United States, and 1,700 of these patients will succumb to the disease. Three out of every four diagnoses will be made in women, and in contrast to many other cancers, the diagnoses are often in younger people between the ages of 20 to 55.

The thyroid is an endocrine gland located in the front of the neck below the ?Adam?s Apple?. It produces the thyroid hormones triiodothyroinine (T3) and thyroxine (T4) in response to hormonal signals from the brain (anterior pituitary gland), which help control the body?s rate of metabolism. It also produces the hormone calcitonin, which helps regulate the amount of calcium in the body.

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There are four general types of thyroid cancer that are commonly seen. The types are distinguished by their cellular pathology:

• Papillary ? 75-85 percent of cases, mostly in young females around age 30-40. It spreads slowly and has an excellent prognosis, with 96-97 percent of patients alive after five years.
• Follicular ? 10-20 percent of cases, more common in women over the age of 50. Still has an excellent prognosis, with 91 percent of patients alive after five years.
• Medullary ? 5-8 percent of cases, is a cancer of cells in the thyroid that produce calcitonin. It requires different treatment than most other thyroid cancers. Overall five-year survival is a bit lower, between 80-85 percent. When present with cancer of the parathyroid gland and adrenal glands, it is referred to as multiple endocrine neoplasia type 2 (MEN-2).
• Anaplastic ? less than 5% of cases, is a dangerous form of thyroid cancer that does not respond to traditional therapies and is likely to quickly metastasize. Only 7-14 percent of patients are alive after five years, and many will succumb within a year of diagnosis.

Risk for developing thyroid cancer is higher for people who have had radiation therapy to the neck, and people who have had radiation therapy as children. Family history of thyroid cancer and chronic goiter are also risk factors.

Symptoms of thyroid cancer can vary by type, but the most common first symptom is the presence of a nodule felt on the neck. These nodules may be benign, however, and biopsy is needed for confirmation. Other symptoms can include cough, difficulty swallowing, the thyroid gland getting bigger, a hoarse or changing voice and swelling of lymph nodes in the neck. Patients with medullary thyroid cancer often also experience diarrhea and flushing due to the excess calcitonin. If the cancer has spread, there may be symptoms related to the target organ, for example bone pain from bone metastases.

Thyroid cancer is definitively diagnosed by biopsy of the suspected cancerous tissue. Most patients will have a fine-needle aspiration for diagnosis; others may need the tissue surgically removed for examination. Additional thyroid nodules deeper in the thyroid are often discovered by ultrasound. Blood tests for thyroid hormones may be abnormal. Some patients will get a radionuclide scan, which can help differentiate between suspicious and benign nodules.

Treatment is usually surgical resection of one lobe of the thyroid or the entire gland. Radioactive iodine-131 is often given to patients after surgery. Any remaining thyroid tissue will take up the radioactive iodine and? be destroyed. However this treatment does not work for medullary thyroid cancer. If the cancer cannot be surgically removed, external radiation is used. The experimental medications Nexavar (sorafenib) and Sutent (sunitinib) are being investigated for possible treatment of thyroid cancer. After treatment, patients will have to take medication to replace the thyroid hormones that are no longer being produced.

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Source: http://www.dailyrx.com/news-article/thyroid-cancer-tumors-grow-foxo3-19927.html

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