From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer

Simple Summary Medullary thyroid cancer derives from calcitonin-producing C cells and is characterized by sporadic and familial RET-mutated forms. Serum calcitonin represents the most reliable and sensitive marker for diagnosis and postsurgical monitoring of medullary thyroid cancer. However, in some patients, calcitonin does not achieve normal levels after surgery leading to misleading diagnosis in terms of outcome and worsening patient management. Therefore, there is a need to find new biomarkers to be used together with serum calcitonin to increase sensitivity and specificity. In this paper, we review the literature from 2010 to 2023 on circulating tumor cells, cell-free DNA, and miRNA and their application in MTC. Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments.