Gene Therapy in Thyroid Cancer

A variety of promising gene therapy approaches have been examined for treatment of follicular cell-derived and medullary thyroid cancer, including corrective gene therapy, cytoreductive gene therapy as well as immunomodulatory gene therapy. In addition, cloning of the NIS gene has provided us with a powerful cytoreductive gene therapy strategy based on targeted NIS gene transfer followed by radionculide (I-131, Re-188, At-211) therapy. The data summarized in this article clearly demonstrate the high potential of currently available gene therapy approaches for future therapy of advanced dedifferentiated and medullary thyroid cancer, in particular as part of a multimodality approach. One of the major hurdles on the way to clinical application of gene therapy approaches in metastasized thyroid cancer is optimal tumor-specific targeting in the presence of low toxicity. Replication-selective viral vectors and novel biodegradable polymers as highly efficient nonviral vectors seem to be most promising candidates for the development of efficient and safe systemic gene therapy strategies. The bystander effect that is associated with some of the above listed gene therapy strategies provides a powerful means to compensate for the limited tumor spread of viral and nonviral vectors. Based on its dual function as therapy and reporter gene allowing noninvasive imaging by I-123-scintigraphy and I-124-PET imaging, NIS gene therapy offers the advantage of detailed characterization of in vivo vector biodistribution as well as localization, level, and duration of transgene expression - an essential prerequisite for exact planning and monitoring of clinical gene therapy trials with the aim of individualized therapy.