Signaling pathways and targeted therapy in high‑risk refractory thyroid cancer: From bench to bedside (Review)

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Thyroid cancer is the most common endocrine malignancy globally, with rising incidence and complex mortality patterns.
• High-risk refractory thyroid cancers present significant clinical management challenges.
• Understanding molecular pathogenesis is crucial for advancing treatment.

Purpose of the Study:

• To systematically review epidemiological trends in thyroid cancer.
• To explore molecular mechanisms of key signaling pathways (MAPK, PI3K/AKT, JAK/STAT, WNT/β-catenin, NF-κB) in thyroid cancer.
• To elaborate on recent advances in targeted therapies for high-risk, refractory thyroid cancer.

Main Methods:

• Systematic review of epidemiological data.
• In-depth exploration of molecular regulatory mechanisms in signaling pathways.
• Review of clinical research on targeted therapies for refractory thyroid cancer.

Main Results:

• Epidemiological trends show increasing thyroid cancer incidence.
• Key signaling pathways (MAPK, PI3K/AKT, JAK/STAT, WNT, NF-κB) play critical roles in thyroid cancer pathogenesis and progression.
• Advances include multikinase inhibitors, BRAF/MEK inhibitors, immunotherapy combinations, and novel targeted/redifferentiation strategies.

Conclusions:

• Targeted therapies offer promising avenues for managing high-risk, refractory thyroid cancers.
• Future directions emphasize a 'total treatment' paradigm and overcoming drug resistance.
• This review serves as a systematic reference for thyroid cancer research and clinical translation.