Targeting Surface Markers in Anaplastic Thyroid Cancer: Future Directions in Ligand-bound Therapy

Anaplastic thyroid cancer (ATC) is the rarest and most aggressive form of thyroid cancer, known for its highly variable nature and poor prognosis, primarily due to the lack of effective treatments. While conventional therapies have had limited success, there remains an urgent need for novel therapeutic approaches to combat this disease. ATC tumors are resistant to the standard radioiodine therapy because they lack the sodium/iodide symporter (NIS), which is necessary for iodine uptake. However, recent advances in theranostics targeting cell surface markers have opened new avenues for treating ATC. We used the PubMed database and Google search engine to identify relevant articles using combinations of specific keywords related to the topic of interest, focusing on each surface marker. This review explores multiple surface markers identified in ATC and their promising roles for delivering therapeutic agents into tumors, inducing cell death. Several promising markers, including prostate-specific membrane antigen, vitamin D receptor, IGF-1 receptor, programmed death-ligand 1, epidermal growth factor receptor, and L-type amino acid transporter 1 (LAT-1), have been found in ATC and could serve as effective targets for delivering therapeutic agents to tumors, inducing cell death. Restoring NIS expression is also explored as a potential therapy for ATC. Additionally, boron neutron capture therapy, which utilizes LAT-1 expression, is highlighted as a future therapeutic option due to its ability to selectively target tumor cells while minimizing damage to surrounding healthy tissue. These strategies offer the potential to overcome many of the challenges associated with ATC, improving patient outcomes and overall survival.