A variety of gene therapy approaches have been evaluated for the treatment of follicular cell-derived and medullary thyroid cancer, including corrective gene therapy (p53 restoration, expression of a dominant negative RET mutant, restoration of PTPη, restoration of Gadd45γ, expression of antisense HMGI[Y]), cytoreductive gene therapy (suicide gene/prodrug strategy HSV-tk/GCV, antiangiogenic therapy with endostatin, ONYX-015, NIS gene transfer followed by 131I therapy) and immunomodulatory gene therapy (expression of IL-2 and IL-12) (Fig. 1, Table 1 ). The data summarized in this review article clearly demonstrate that the currently available strategies represent promising novel therapeutic approaches for future gene therapy of advanced thyroid cancer. The combination of different therapeutic genes seems to be useful to enhance therapeutic efficacy as shown for the combination of the HSV-tk/GCV system with IL-2 gene transfer. The clinical efficacy of gene therapy, however, is not only determined by the potency of therapeutic genes, but also by the efficiency of vector-mediated gene delivery. Currently available vector systems reveal various problems limiting their safety and efficiency, such as significant first pass effect in the liver, increased toxicity by vector leakage, neutralization by host immunity, poor tissue distribution and low infectivity. Close collaboration of creative molecular biologists and clinical scientists will therefore be required to address these problems and to develop efficient gene delivery systems by optimized, systemically administered vectors. However, until the perfectly targeted and safe vector system is developed, the choice of therapeutic gene will be crucially important to compensate for the deficiencies of the vectors that are currently available. For the foreseeable future it is unlikely that any gene therapy strategy available would cure patients with advanced dedifferentiated and medullary thyroid cancer when given as a single agent. However, currently available data strongly suggest that gene therapy, in particular the combination of therapeutic genes, will have a promising role at least as part of a multimodality approach.
This work was supported by a grant to C. Spitzweg (Sp 581/31) from the German Research Council (Deutsche Forschungsgemeinschaft, Bonn, Germany).
Christine Spitzweg, M.D., Klinikum Grosshadern, Medizinische Klinik II, Marchioninistrasse 15, 81377 Muenchen, Germany. E-mail: Christine.Spitzweg@med.uni-muenchen.de.
Thyroid. 2004;14(6) © 2004 Mary Ann Liebert, Inc.
Cite this: Gene Therapy for Thyroid Cancer: Current Status and Future Prospects - Medscape - Jun 01, 2004.