Abstract
<jats:p>Thyroid cancer management traditionally includes surgery and radioactive iodine, but advanced or RAI-refractory cases require systemic therapies. Multikinase inhibitors, including sorafenib, lenvatinib, vandetanib, and cabozantinib, target diverse pathways such as VEGFR1–3, FGFR1–4, PDGFRα, RET, KIT, and RAS/RAF/MEK/ERK. These agents inhibit tumor proliferation and angiogenesis, demonstrating significant improvements in progression-free survival in both differentiated and medullary thyroid cancers. Recent trials have also introduced novel MKIs such as apatinib, anlotinib, and donafenib, expanding therapeutic options. However, resistance mechanisms, including activation of alternative proangiogenic pathways, limit long-term efficacy. To overcome these barriers, combination regimens with immune checkpoint inhibitors are being explored, showing early promise. Angiogenesis plays a pivotal role in thyroid cancer progression, driven by VEGF/VEGFR signaling, hypoxia, and HIF-mediated pathways. Agents such as anlotinib and apatinib suppress proliferation, migration, and angiogenesis in thyroid cancer cell lines and xenograft models. Natural compounds, including asiaticoside and emodin, also inhibit TRAF6, HIF-1α, and VEGF, reducing tumor growth. Targeting hypoxia-inducible factors with agents such as echinomycin and temsirolimus offers additional therapeutic potential. Clinical analyses suggest that while antiangiogenic monotherapy has limited efficacy in anaplastic thyroid cancer, combination with chemotherapy, radiotherapy, or immunotherapy may enhance outcomes.</jats:p>