Thyroid is a part of the endocrine system responsible for the production of various hormones that controls essential functions such as the heart, body temperature and the digestion. Thyroid cancer involves the thyroid gland which has two main types of cells; the follicular cells and C cells (parafollicularcells). The follicular cells absorb the iodine from the blood and produces thyroid hormones and the C cells are responsible for the production of calcitonin, a hormone necessary to control the calcium level in the body. There are many types of tumors that develop in the thyroid gland some of which are cancerous and others benign. However, it is important to determine the type of tumor so treatment accordingly can be initiated. The diagnosis for thyroid cancer is based on the biopsy and most of them can be treated successfully although advanced cancer can be challenging  particularly if they do not respond to radioactive iodine therapy. According to the American Cancer Society, in 2018, the number of cases for thyroid cancer is estimated to be 53,990 and about 2,060 deaths from thyroid cancer.

Benign Thyroid and Nodules

The enlargement of thyroid does not necessarily indicate cancer and can occur because of abnormality in certain hormones. The abnormal swelling of thyroid is called goiter and the presence of any lumps in the thyroid gland is known as thyroid nodules. In most of the cases, thyroid nodules are benign but can cause hyperthyroidism. Some of the different types of thyroid nodules are thyroid cysts, inflammatory nodules, multinodular goiter, hyperfunctioning thyroid nodules and thyroid cancer. One of the biggest concerns with thyroid nodules is cancer which is considered to be less than 5%. Generally, thyroid nodules don’t require treatment provided they are not causing symptoms.

Malignant Thyroid Tumors

Some of the types of malignant tumors include; differentiated (such as papillary, follicular), medullary and anaplastic (an aggressive undifferentiated tumor).

Differentiated thyroid cancer: Most of thyroid cancers are differentiated thyroid cancer. Papillary cancer usually develops very slowly, located in one lobe of the thyroid gland and are rarely fatal. Follicular cancer is common among individuals not getting sufficient iodine in their diet and the prognosis is not as good as papillary cancer. Hurthle cell cancer is a type of cancer that is difficult to detect and treat.

Medullary thyroid cancer: It accounts for about 4% of thyroid cancer and are difficult to detect and treat. The two types of medullary thyroid cancer are sporadic and familial meaning it is inherited.

Anaplastic thyroid cancer: Considered a deadly disease with poor prognosis, it is a rare form of cancer accounting for about 2% of thyroid cancer.

Contributing factors associated with thyroid cancer

Dietary iodine appears to play a role with thyroid cancer as higher frequency is associated with high dietary iodine and the development of papillary thyroid cancer whereas the iodine deficient countries presents higher incidence of follicular thyroid cancer. Also, other dietary factor such as the intake of carcinogen is also believed to play causative roles. Further, TSH level has been associated with an increased risk of developing cancer as those with high TSH with thyroid nodular disease are at increased risk of differentiated thyroid cancer and advanced tumor stage.

Receptor tyrosine kinase RET

During the last decade several studies have been conducted to identify genetic alterations associated with thyroid tumors. RET protooncogene is involved in the regulation of growth, survival and migration of cells. There are more than ten rearrangements of the RET gene, known as RET/PTC rearrangement, however, RET/PTC1, RET/PTC2 and RET/PTC3 accounts for the majority of rearrangements identified in papillary thyroid carcinoma (PTC). RET mutations mostly is involved in the medullary thyroid cancers (MTCs). Until recently, MKIs (multikinase inhibitors) with nonselective RET inhibitor activity have been available for individuals with RET-altered cancers. However, the nonselective RET inhibitors shows only modest activity in RET-mutated MTCs. In contrast to MKIs, a novel LOXO-292 possesses potency against diverse RET alterations and favorable PK properties.

Multiple Endocrine Neoplasia type 2A and associated risk for thyroid cancer

Multiple Endocrine Neoplasia type 2A (MEN 2A) is one of the genetic syndrome where most of the affected individual can develop thyroid cancer at some point in their life and parathyroid adenomas resulting in hyperparathyroidism. The 2015 American Thyroid Association (ATA) guidelines for management of medullary thyroid cancer categorized this genetic mutations into three groups; low, moderate and high risk. Accordingly, a study was done to determine the implications of high risk verses moderate risk of developing cancer with the mutation. It involved 262 MEN2 patients which observed the overall survival and the time involved in the development of medullary thyroid cancer. The study confirms the ATA recommendation that the high-risk mutation group did develop cancer therefore a surgery is required to remove the thyroid at a younger age.

Various therapeutic agents

Surgery is the most effective treatment option for most of the thyroid cancer with thyroidectomy. Research is identifying the different cancers that are most likely to recur after surgery and those patients could be helped by receiving radioactive iodine therapy. Recent studies have indicated that individuals with very low thyroglobulin levels 3 months after surgery show low risk of recurrence. Chemotherapy drugs such as paclitaxel and other drugs are being studied along with the effects of chemotherapy and radiation as a combined treatment for anaplastic thyroid cancer. Targeted therapies can attack specific targets on tumor cells and these include kinase inhibitors to treat cancer with mutations in genes such as BRAF and RET/PTC, anti-angiogenesis drugs works by disrupting the development of new blood vessels  for tumor growth and other targeted drugs. Among patients with ATC, adjuvant therapy in the form of external beam radiation or chemotherapy should be initiated soon as patient recovers from surgery. The study indicates that multimodal therapy with a combination of surgery and definite external beam radiation shows better survival rates.

Also, as individuals with advanced medullary thyroid cancer don’t respond well with radioactive iodine therapy therefore treatment for advanced or recurrent medullary thyroid cancer has proven to be challenging until recently. Although not a curative, in a clinical trial, lenvatinib has shown improved progression-free survival for these patients and also been approved by the FDA for the use in papillary and follicular thyroid cancer.