Abstract
Thyroid cancer, a prevalent endocrine malignancy with rising global incidence, encompasses four primary subtypes: Papillary (PTC), follicular (FTC), medullary (MTC) and anaplastic thyroid carcinoma (ATC). PTC, accounting for 85-90% of cases, is primarily driven by BRAF V600E mutations alongside dysregulated non-coding RNAs, such as long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 and microRNA (miR)-1270. These alterations collectively activate MAPK signaling, promoting tumorigenesis. Furthermore, PTC exhibits metabolic reprogramming characterized by dysregulated glucose and lipid metabolism, where tumor suppressors, including family with sequence similarity 111 member B and fat mass and obesity-associated genes, constrain glycolytic flux. FTC, characterized by Ras mutations, exhibits enhanced lipid metabolism and PI3K/AKT pathway activation. Methyltransferase-like protein 16 and sclerostin domain-containing protein 1 have been highlighted as regulators of FTC progression. MTC, associated with rearranged during transfection (RET) proto-oncogene mutations, demonstrates programmed cell death protein-1/programmed death ligand-1 pathway involvement, which offers potential immunotherapy targets. ATC, the most aggressive subtype, is characterized by recurrent genetic alterations such as telomerase reverse transcriptase promoter and tumor protein p53 mutations, cAMP-responsive element-binding protein 3-like 1-driven activation of cancer-associated fibroblasts and hematological and neurological expressed 1-stathmin 1 signaling-mediated invasiveness. Recent diagnostic innovations encompass serum biomarkers, such as stanniocalcin-1, microRNA signatures (including miR-26b-5p) for PTC and MTC detection, radiomics-based differentiation of ATC from other subtypes and optical imaging techniques for precision diagnosis. Molecularly targeted therapies constitute the cornerstone of current strategies, with vemurafenib inhibiting BRAF/MEK in PTC, sorafenib acting as a multikinase suppressor in FTC, vandetanib blocking RET in MTC and berberine-doxorubicin combinations overcoming chemoresistance in ATC. Metabolic interventions, including metformin for glucose modulation in PTC and novel delivery systems such as micelle-encapsulated AB3 for MTC, demonstrate translational potential. The present review summarizes molecular mechanisms, diagnostic tools and emerging therapies while emphasizing the necessity of subtype-specific approaches to improve clinical outcomes in thyroid oncology.