Overview

The thyroid is a butterfly-shaped organ located in the front of the neck and participates in the control of an array of bodily functions by secreting thyroid hormones. This organ is responsible for forming and secreting thyroid hormones. These hormones generally increase the function and metabolism of most nucleated cells in our body. Thyroid-stimulating hormone (TSH) is made by the pituitary gland and circulates the bloodstream to monitor the levels of the thyroid hormones.¹ An example of when the concentration of a thyroid hormone is lowered is during intense exercise. They can activate myogenic regulatory factors, a group of proteins that are essential for muscle regeneration and growth.²

Since the thyroid is such an influential organ, the development of thyroid cancer can have complex and detrimental downstream consequences. This article will explore how thyroid cancer can manifest and possible therapeutic targets.

What is thyroid cancer?

Thyroid cancer is a malignancy which stems from the parenchymal cells of the thyroid. There are two major types of parenchymal cells; thyroid follicular cells, which can induce differentiated thyroid cancer (DTC), and parafollicular cells, which give rise to medullary thyroid carcinoma (MTC). 

The most abundant cells found in the thyroid are the follicular cells. These cells are the most vulnerable to precancerous mutations. Therefore, DTCs such as follicular thyroid cancer, Hurthle cell cancer, and papillary thyroid cancer account for 90-95% of all thyroid malignancies. On the other hand, parafollicular cells account for less than 1% of the follicular cells in the thyroid. Hence, cancer stemming from this cell type only accounts for 1-2% of cases.³

Causes and risk factors for thyroid cancer

The causes and risk factors for thyroid cancer include:⁴

• Family history of thyroid cancer
• Radiation exposure (specifically to the head and neck region)
• Iodine deficiency 
• Smoking
• Environmental pollutants (industrialised food additives in food and vegetables, and polybrominated diphenyl ethers - a chemical used in building materials and plastics)

Most of these factors increase the likelihood of genetic mutations that can cause the uncontrolled growth of parenchymal cells and eventually a malignant tumour. 

In the UK, the incidence of thyroid cancer is approximately 3 times higher in people assigned female at birth (AFAB) compared to people assigned male at birth (AMAB). However, in England, those AFAB have historically had a greater ten-year survival rate from thyroid cancer than those AMAB.⁵

Signs and symptoms of thyroid cancer

The signs and symptoms of thyroid cancer may include:³

• Difficulty breathing and swallowing
• A lump in the neck
• Voice changes (weaker or raspy)
• Fever
• Unexpected weight loss

Current standard treatments for thyroid cancer

Surgery 

A thyroidectomy is the most common surgery for thyroid cancer. It can involve removing the entire gland (total thyroidectomy) or a partial removal of the gland (near-total thyroidectomy). This means the patient would have to take thyroid hormones daily, as the thyroid would usually produce them.⁶

Radioactive iodine therapy

Due to the thyroid’s strong affinity for iodine, this characteristic can be effectively exploited in this treatment strategy. Radioactive iodine therapy can help deliver radiation, destroying overactive thyroid tissue or cancer cells  This treatment method is highly effective against well-differentiated thyroid cancer (cancer cells that look like normal cells), significantly improving patient prognosis. However, patients may experience adverse effects depending on the dosage they receive, such as nausea, vomiting, chest pain, and anaemia.⁷

Hormone therapy

This is also known as TSH-suppression therapy. Drugs such as levothyroxine are often prescribed to ensure there is a sufficient concentration of thyroid hormones in the body so that the pituitary gland is not stimulated to synthesise and secrete TSH. This treatment method has been strongly associated with a longer survival of patients with thyroid disorders.⁸

Targeted therapies

Targeted therapies refer to a method of cancer treatment that employs drugs to target specific molecules that otherwise contribute to the uncontrolled growth of cancer cells. This treatment is often chosen when standard treatments are ineffective, when the cancer has specific genetic mutations, or when the cancer has spread to other parts of the body (metastasis).

They have a wide range of applications, such as:

• Preventing signals that allow cancer cells to divide
• Block signals that would allow for blood vessel formation (angiogenesis)
• Restore programmed cell death (apoptosis)
• Helping the immune system recognise and destroy cancer cells (monoclonal antibodies)

With regards to thyroid cancer specifically, several molecular alterations have been identified to induce several hallmarks of cancer - the biological capabilities that are acquired to develop a tumour. This has allowed for the development of drugs that work to restore normal cell activity by combating the hallmarks of cancer.⁹

Larotrectinib 

Laroreectnib acts as an inhibitor, preventing the activity of an enzyme called tyrosine kinase. This enzyme plays a significant role in several cancers by instructing cells to grow, divide or carry out other functions that promote the growth of a tumour. The inhibition of these oncogenic processes by larotrectinib kills cancer cells. Recent studies have shown that this drug has continued to show a quick and long-lasting response, enabling patients to experience extended survival.¹⁰

Dabrafenib

Dabrafenib is another kinase inhibitor, specifically inhibiting a protein called BRAF kinase. BRAF has been seen to mutate in 36-86% of patients with papillary thyroid cancer and 20-25% of patients with anaplastic thyroid carcinoma.¹¹ Studies have shown dabrafenib is an effective drug against patients with the BRAF mutation, reducing 64% of patients’ tumour size by at least 10%.¹² This treatment method has also been reported to be well tolerated and patients generally experienced mild, but manageable toxicity.

FAQs

How can thyroid cancer be diagnosed?

Diagnosis of thyroid cancer can be performed by:³

• Physical examination - the presence of neck lymph nodes (swelling) and firmness of the nodule are suspicious characteristics of malignancy and would result in further evaluation (most likely CT or MRI scans)
• Molecular testing - gene mutation profiling panels can be used to detect genes that are associated with thyroid cancer since they account for ~70% of thyroid cancer cases
• Biopsy - a fine needle is inserted into the thyroid nodule. A syringe is used to pull cells out for examination. Scientists will then stage and grade these cells, which tells us the overall appearance of the cells, the size of the tumour, and if the tumour is likely to spread (metastasise)

How long can you live with a cancerous thyroid nodule?

Over 85% of people with AMAB survive cancer for 5 years or more, and approximately 95% of people with AFAB survive their cancer for at least 5 years from diagnosis. Since 99.2% of patients in England between 15-44 survive thyroid cancer for at least 10 years, the age of the patient heavily influences the likelihood of survival, in comparison to 57.7% of people diagnosed between the ages of 75-99.¹³

Is thyroid cancer curable?

This is entirely dependent on the type of thyroid cancer. DTCs such as papillary and follicular thyroid cancer are highly treatable and generally cureable. Conversely, poorly differentiated tumours, while less common (such as anaplastic thyroid cancer) are more aggressive and tend to metastasize quickly. Therefore, once symptoms arise, it is important to see a doctor immediately. 

When is targeted therapy used for thyroid cancer?

It is often used if the tumour has spread to other parts of the body and is not responding to traditional treatments such as thyroidectomy or is resistant to radioactive iodine. Therefore, this treatment method applies to patients who have a tumour that threatens the function of other organs or continues to grow despite standard therapies. 

If the patient has undergone molecular screening and known genetic mutations have been identified, then an oncologist would likely consider this treatment method above standard therapies.

Summary

The thyroid is involved with a plethora of bodily functions, and thyroid cancer can manifest into a variety of symptoms. Symptoms such as voice changes, difficulty swallowing or breathing, and unexpected weight loss are the most common. A diagnosis can be made after a blood test, an ultrasound, or a biopsy. Current treatment methods involve radioactive iodine therapy, hormone replacement therapy, and targeted therapies, all of which have proved to be effective, but not all without adverse effects. 

Despite the fact that the exact causes of thyroid cancer have not been identified, the risk of developing this disease can be lowered by leading a healthy lifestyle and avoiding radiation exposure.