Opportunities and Challenges of Liquid Biopsy in Thyroid Cancer

Abstract

Thyroid cancer is the most common malignancy of the endocrine system, encompassing different entities with distinct histological features and clinical behavior. The diagnostic definition, therapeutic approach, and follow-up of thyroid cancers display some controversial aspects that represent unmet medical needs. Liquid biopsy is a non-invasive approach that detects and analyzes biological samples released from the tumor into the bloodstream. With the use of different technologies, tumor cells, free nucleic acids, and extracellular vesicles can be retrieved in the serum of cancer patients and valuable molecular information can be obtained. Recently, a growing body of evidence is accumulating concerning the use of liquid biopsy in thyroid cancer, as it can be exploited to define a patient’s diagnosis, estimate their prognosis, and monitor tumor recurrence or treatment response. Indeed, liquid biopsy can be a valuable tool to overcome the limits of conventional management of thyroid malignancies. In this review, we summarize currently available data about liquid biopsy in differentiated, poorly differentiated/anaplastic, and medullary thyroid cancer, focusing on circulating tumor cells, circulating free nucleic acids, and extracellular vesicles.

MANAGEMENT OF ENDOCRINE DISEASE: Medullary thyroid cancer: from molecular biology and therapeutic pitfalls to future targeted treatment perspectives

“…Molecular profiling by next-generation sequencing (NGS) offers crucial information regarding the tumor mutational burden not only for the selection of the most appropriate targeted therapy but also for the prediction of possible drug resistance (61). Moreover, liquid biopsy is a non-invasive diagnostic approach which can assist tailor-made treatment plan by assessing the circulating free nucleic acids (cf-DNA, cf-RNA, mi-RNA), circulating tumor cells (CTCs) and tumor-derived extracellular vesicles (EVs) in the blood; this method may thus provide a realtime snapshot of tumor molecular identity and may reveal possible genetic alterations responsible for drug resistance (62,63,64).…”

The Autoantibodies against Tumor-Associated Antigens as Potential Blood-Based Biomarkers in Thyroid Neoplasia: Rationales, Opportunities and Challenges

“…As compared with the traditional tumor markers and the diagnostic targets of the liquid biopsy (e.g., circulating tumor cells, cell-free tumor DNA/RNA, etc.) (reviewed in [ 20 , 21 ]), the TAA-AAbs are characterized by a set of unique properties rendering them particularly suitable for some of the diagnostic applications but significantly limiting their use in others [ 10 , 11 , 12 ].…”

Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?

“…For example, NETest, based on the detection of circulating tumor transcripts, is finding application in the diagnosis of gastrointestinal neuroendocrine tumors (GEP-NENs) [ 38 ]. For MTCs, liquid biopsies allow the analysis of circulating microRNAs (miRNAs) and cell-free DNA (cf-DNA) [ 39 ].…”

“…Cf-DNA finds application both in the diagnosis of MTCs and in assessing prognosis and response to treatment. In the case of Ctn-negative lesions, cf-DNA works well as a diagnostic biomarker [ 39 ]. Cote et al [ 42 ] proved the feasibility of using cf-DNA to detect M918T mutations in MTCs.…”