By Dr Nicola Davies Thyroid cancer is a rare cancer that encompasses several variations (Table 1).1-3 The incidence is higher in women compared to men.4 Worldwide, the most common age at onset is between 15 and 49 years in females, compared to 50 and 69 years in males.5 However, the reasons behind this disparity are not fully understood. Table 1. Types of thyroid cancer Type of Thyroid Cancer Characteristics Papillary Most common type, slow-growing,…

By Dr Nicola Davies

Thyroid cancer is a rare cancer that encompasses several variations (Table 1).^1-3 The incidence is higher in women compared to men.⁴ Worldwide, the most common age at onset is between 15 and 49 years in females, compared to 50 and 69 years in males.⁵ However, the reasons behind this disparity are not fully understood. 

Table 1. Types of thyroid cancer

Type of Thyroid Cancer	Characteristics
Papillary	Most common type, slow-growing, develops from follicular cells, may spread to nearby lymph nodes.
Follicular	Found more frequently in countries with an inadequate dietary intake of iodine. More aggressive than papillary cancer and more likely to spread to other organs.
Anaplastic	Most undifferentiated type, very aggressive, quickly spreads to other parts of the neck and body.
Medullary	Develops from C-cells, more aggressive and less differentiated than papillary or follicular cancers.
Hürthle cell	A rare subtype of follicular carcinoma, accounts for fewer than 5% of all thyroid cancers.
Poorly differentiated	More aggressive than well-differentiated types, but not as aggressive as anaplastic thyroid cancer.
Thyroid sarcoma or lymphoma	Very rare types that originate from cells other than the thyroid’s follicular or C cells.

While treatment regimens for thyroid cancer are well-established and associated with excellent survival outcomes,⁶ there is ongoing research to further improve therapeutic options and reduce the financial burden on patients.⁷ This September, which is Thyroid Cancer Awareness Month, we explore the most promising new pharmacological options for thyroid cancer and what the future may hold.

Current treatment regimens

The current standard treatment for thyroid cancer involves a combination of surgery, radioactive iodine therapy, and thyroid hormone replacement therapy (HRT). Surgery, typically a total or partial thyroidectomy, is performed to remove the cancerous tissue.⁶ Radioactive iodine therapy is used to destroy any remaining thyroid cells and prevent the production of excessive thyroid hormones.⁸ Thyroid HRT, usually with levothyroxine (LT4), is administered to replace the thyroid hormone production in patients who have undergone thyroidectomy.⁹

Breakthroughs in the management of thyroid cancer

Pharmacological treatments for thyroid cancer have made significant progress in recent years, with the development of targeted therapies and the identification of key signaling pathways involved in pathogenesis.^{10, 11} These advancements have led to improved disease control and treatment options for patients with thyroid cancer. 

Targeted therapies

One of the major breakthroughs in pharmacological treatment for thyroid cancer is the use of targeted therapies, such as tyrosine kinase inhibitors (TKIs), which specifically target the signaling pathways involved in thyroid oncogenesis. TKIs have shown effectiveness in controlling disease and have become an important component of systemic therapy for thyroid cancer.¹⁰

For example, larotrectinib (Vitrakvi; from Bayer [BAYN: DE]) and entrectinib (Rozlytrek from Roche [ROG: SIX]), which are neurotrophic tropomyosin receptor kinase (NTRK) inhibitors, have demonstrated excellent disease control and are approved for frontline systemic treatment of thyroid cancers harboring NTRK-fusion alterations.¹² Additionally, multikinase inhibitors like vandetanib (Caprelsa; from Sanofi [Euronext: SAN]), cabozantinib (Cabometyx; from Exelixis [Nasdaq: EXEL]), lenvatinib (Lenvima; from Eisai [TYO: 4523]), and sorafenib (Nexavar; from Bayer), have been used as first-line treatments for advanced thyroid cancer.^{13, 14}

Another area of progress is the use of targeted therapies for specific genetic alterations. For example, selective RET (rearranged during transfection) inhibitors like selpercatinib (Retevmo; from El Lilly [NYSE: LLY}) have shown promising results in treating RET-altered thyroid cancer.¹³ These targeted therapies offer personalized treatment options based on the specific genetic profile of the tumor, leading to improved outcomes for patients.

Vitamin D

Vitamin D, specifically the form D3, has several beneficial effects against cancer progression. In one study, two thyroid cancer cell lines were treated with varying concentrations of 1,25-OH-vitamin D3.¹⁵ The researchers assessed cell viability, cell migration, and measured the levels of CCL2 and CXCL8 in the cell culture supernatants. The results showed that vitamin D did not affect cell viability but significantly reduced the migration of thyroid cancer cells in a dose-dependent manner.

Additionally, vitamin D had different effects on the secretion of CCL2 and CXCL8. It significantly inhibited the secretion of CCL2 in both thyroid cancer cell lines and inhibited the secretion of CXCL8 only in one of the cell lines, called TPC-1. Further studies are needed to better understand the specific pathways involved in the inhibitory effects of vitamin D on CCL2 and CXCL8 in thyroid cancer cells.

The emergence of nanomedicine

The use of nanomedicines has been explored in the treatment of cancer, with potential applications in the management of thyroid disorders.⁶ Nanoparticles allow for targeted drug delivery, sustained drug release, and enhancement of immunotherapy. Pre-clinical studies have shown encouraging results, but further research is needed to address challenges and optimize the clinical translation of nanomedicines for thyroid cancer treatment.

What does the future hold?

Despite these advancements, challenges remain in the pharmacological treatment of thyroid cancer. Some patients with advanced or metastatic thyroid cancer do not respond well to current treatments, highlighting the need for further research and the development of novel therapeutic strategies.^16,17

Additionally, the long-term health-related quality of life outcomes for thyroid cancer survivors requires greater attention in pharmacological development.¹⁸ Still, with continued funding, advocacy, and medical innovation, we are getting closer to better outcomes and longer lives for those with this thyroid cancer.

References

1. Vuong, H.G., Le, M., Hassell, L., Kondo, T. and Kakudo, K. (2022). The Differences in Distant Metastatic Patterns and Their Corresponding Survival between Thyroid Cancer Subtypes. Head & Neck, 44(4), pp.926–932. doi:https://doi.org/10.1002/hed.26987.
2. Tiucă, R.A., Tiucă, O.M. and Pascanu, I. (2023). The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update. Biomedicines, 11(4), pp.1075–1075. doi:https://doi.org/10.3390/biomedicines11041075.
3. Bai, Y., Kakudo, K. and Jung, C.K. (2020). Updates in the Pathologic Classification of Thyroid Neoplasms: A Review of the World Health Organization Classification. Endocrinology and Metabolism, [online] 35(4), pp.696–715. doi:https://doi.org/10.3803/EnM.2020.807.
4. Lam, D., Davies, L. and Sawka, A.M. (2022). Women and Thyroid Cancer incidence: Overdiagnosis versus Biological Risk. Current Opinion in Endocrinology, Diabetes & Obesity, Publish Ahead of Print. doi:https://doi.org/10.1097/med.0000000000000756.
5. Deng, Y., Li, H., Wang, M., Li, N., Tian, T., Wu, Y., Xu, P., Yang, S., Zhai, Z., Zhou, L., Hao, Q., Song, D., Jin, T., Lyu, J. and Dai, Z. (2020). Global Burden of Thyroid Cancer From 1990 to 2017. JAMA Network Open, [online] 3(6). doi:https://doi.org/10.1001/jamanetworkopen.2020.8759.
6. Pund, S., Chandak, R., Rajurkar, V., Kharat, N., Khalil, S.S.S., Shaikh, S., Parve, K., Kadam, M., Choudante, S., Pulate, C., Wakale, V. and Tare, H. (2022). A Review on Nanomedicines in Treatment of Thyroid And Their Applications in Management of Thyroid Disorders. International journal of health sciences, pp.11141–11154. doi:https://doi.org/10.53730/ijhs.v6ns5.10936.
7. Xiao, R., Rathi, V.K., Gross, C.P., Ross, J.S. and Sethi, R.K.V. (2021). Payer-Negotiated Prices in the Diagnosis and Management of Thyroid Cancer in 2021. JAMA, 326(2), p.184. doi:https://doi.org/10.1001/jama.2021.8535.
8. Ringel, M.D. (2021). Radioiodine: 80 Years and Counting; the Past, Present, and Future. Endocrine-Related Cancer, 28(10), pp.E3–E4. doi:https://doi.org/10.1530/erc-21-0234.
9. Ilaria Stramazzo, Capriello, S., Antonelli, A., Fallahi, P., Centanni, M. and Virili, C. (2022). Seeking optimization of LT4 treatment in patients with differentiated thyroid cancer. Hormones, 21(4), pp.537–543. doi:https://doi.org/10.1007/s42000-022-00376-9.
10. Babu, G., Kumar, R., Rafi, M., Nair, L., Sharafuddin, Z., Mathew, J., Jose, N. and Kainickal, C.T. (2022). Systemic Therapy in Thyroid Cancer. IntechOpen eBooks. doi:https://doi.org/10.5772/intechopen.106462.
11. Valderrabano, P., Eszlinger, M., Stewardson, P. and Paschke, R. (2023). Clinical Value of Molecular Markers as Diagnostic and Prognostic Tools to Guide Treatment of Thyroid Cancer. Clinical Endocrinology. doi:https://doi.org/10.1111/cen.14882.
12. Shonka, D.C., Ho, A.L., Chintakuntlawar, A.V., Geiger, J.L., Park, J.C., Seetharamu, N., Jasim, S., Ahmed, Bible, K.C., Brose, M.S., Cabanillas, M.E., Kirsten, Davies, L., Dias-Santagata, D., Fagin, J.A., Faquin, W.C., Ghossein, R., Gopal, R.K., Miyauchi, A. and Nikiforov, Y.E. (2022). American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group consensus statement on mutational testing in thyroid cancer: Defining advanced thyroid cancer and its targeted treatment. Head & neck, 44(6), pp.1277–1300. doi:https://doi.org/10.1002/hed.27025.
13. Baek, H.-S., Ha, J., Ha, S., Bae, J.S., Jung, C.K. and Lim, D.-J. (2023). Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea. Current Oncology, 30(3), pp.3020–3031. doi:https://doi.org/10.3390/curroncol30030229.
14. Zafon, C. and Fernández, B.C. (2022). Use of Multikinase inhibitors/lenvatinib in Singular Thyroid Cancer Scenarios. Cancer Medicine, 11(S1), pp.3–4. doi:https://doi.org/10.1002/cam4.5154.
15. Coperchini, F., Greco, A., Croce, L., Petrosino, E., Grillini, B., Magri, F., Chiovato, L. and Rotondi, M. (2022). Vitamin D Reduces Thyroid Cancer Cells Migration Independently from the Modulation of CCL2 and CXCL8 Chemokines Secretion. Frontiers in Endocrinology, 13. doi:https://doi.org/10.3389/fendo.2022.876397.
16. Avagliano, A., Fiume, G., Bellevicine, C., Troncone, G., Venuta, A., Acampora, V., De Lella, S., Ruocco, M.R., Masone, S., Velotti, N., Carotenuto, P., Mallardo, M., Caiazza, C., Montagnani, S. and Arcucci, A. (2022). Thyroid Cancer and Fibroblasts. Cancers, 14(17), p.4172. doi:https://doi.org/10.3390/cancers14174172.
17. Huang, N., Wang, Y., Wei, W.-J., Xiang, J., Chen, J., Guan, Q., Wang, Y., Lu, Z., Ma, B., Hu, J.-Q., Wang, Y. and Ji, Q. (2022). A Systematic Review of Neoadjuvant Targeted Therapy in Locally Advanced Thyroid Cancer. Holistic Integrative Oncology, 1(1). doi:https://doi.org/10.1007/s44178-022-00016-7.
18. Blefari, N.D.A., Rowe, C.W., Wiadji, E., Lambkin, D., Carroll, R., Fradgley, E.A. and O’Neill, C.J. (2022). Long-Term Health-Related Quality of Life Outcomes following Thyroid Surgery for Malignant or Benign Disease: Deficits Persist in Cancer Survivors beyond Five Years. World Journal of Surgery, [online] 46(10), pp.2423–2432. doi:https://doi.org/10.1007/s00268-022-06643-5.