Potentially New Therapies in Thyroid Cancer

Jin-Woo Park, MD ■ Quan-Yang Duh, MD ■ Orlo H. Clark, MD

Differentiated thyroid cancer (DTC) of follicular cell origin is a fascinating tumor because of its varying aggressiveness. Fortunately, most patients with these cancers, despite regional metastasis, can be cured by surgical resection, radioiodine ablation, and thyroid-stimulating hormone (TSH) suppression therapy. Unfortunately, patients with poorly differentiated thyroid cancers or anaplastic thyroid cancers usually fail to respond to this combined therapy. These tumors usually grow rapidly, invade adjacent structures, and spread to other parts of the body. During the dedifferentiation process, they lose thyroid-specific gene expressions, including the ability to take up and organify radioiodine and to make thyroglobulin (TG). The methods used to treat patients with DTC are therefore usually not effective in these patients. These tumors also usually fail to respond to alternative treatment with external radiation or systemic cancer chemotherapy. Medullary thyroid carcinomas are also highly aggressive, and there is no alternative if patients do not respond to surgical treatment. We therefore need to develop novel treatments for these unfortunate patients.

Advances in molecular and cellular biology make it possible to develop new therapeutic approaches to thyroid cancer. These approaches can be divided largely into two categories regarding treatment targets. Redifferentiation therapy targets thyroid-specific genes to restore thyroid-specific differentiated function and to make the tumors respond to conventional therapy. The other possible category of treatment targets several cancer-related genes or their products that do not depend on thyroid-specific genes but depend on altered characteristics of thyroid cancer cells during tumorigenesis (Fig. 35-1).

Therapeutic approaches described in this chapter have established effects in vitro, but the majority of them are not ready for medical practice yet. Careful clinical trials and analyses should be performed.

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