Introduction: Thyroid malignant tumors represent a heterogeneous group of disorders marked by significant genetic and phenotypic variability, resulting in diverse clinical presentations and prognostic outcomes. The distinction between well-differentiated cancers, such as papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), and more aggressive forms like poorly differentiated and anaplastic thyroid carcinoma necessitates a deep understanding of their molecular foundations. This knowledge is crucial for refining diagnostic approaches and informing targeted therapeutic interventions that can substantially improve patient outcomes.
Methods: This narrative review synthesizes findings from an extensive analysis of recent peer-reviewed literature focused on the genetic and molecular characteristics of thyroid cancers. Key molecular features, including oncogenic mutations, gene expression profiles, and emerging biomarkers, were evaluated for their implications in diagnosis, prognosis, and therapeutic modalities.
Results: Our analysis underscores several pivotal genetic alterations associated with thyroid tumors:
_TERT Promoter Mutations: Frequently associated with aggressive variants of PTC, these mutations serve as critical prognostic indicators (Xing et al., 2014).
_BRAF Mutations: Notably, the BRAF V600E mutation significantly influences treatment outcomes, supporting its role as a therapeutic target (Namba et al., 2016).
_RAS Mutations and PAX8-PPAR Gamma Rearrangements: Common in FTC, these alterations play vital roles in tumor progression and prognostic evaluation (Tufano et al., 2015).
_Anaplastic thyroid carcinoma is characterized by a high mutational burden, including mutations in TP53, BRAF, and TERT, which often confer resistance to conventional therapies, highlighting the urgent need for innovative treatment strategies (Liu et al., 2018).
_Emerging molecular biomarkers, such as microRNAs and circulating tumor DNA (ctDNA), have proven invaluable for non-invasive diagnostics and monitoring disease progression. Specific microRNA expression profiles correlate with tumor aggressiveness and therapeutic resistance, indicating their potential as targets for novel therapeutic interventions (Kumar et al., 2019).
_Comprehensive genomic profiling has revealed alterations in pathways regulating cell proliferation, apoptosis, and immune evasion, thereby identifying new therapeutic targets that can be leveraged in precision medicine.
Conclusion: As our understanding of molecular alterations in thyroid cancers evolves, integrating these insights into clinical practice holds significant promise for enhancing prognostic accuracy and facilitating the development of personalized therapeutic interventions. This review emphasizes the critical role of molecular diagnostics in refining the management of thyroid cancer and highlights the potential for pioneering treatment strategies tailored to the unique molecular characteristics of individual tumors. Future research should prioritize the translation of these molecular insights into clinical protocols to optimize patient outcomes and advance the field of targeted therapies.