Thyroid Cancer Gene Therapyt with Molecular Targeting by Radio-responsing genes

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Thyroid follicular cell-derived carcinomas are classified pathologically as differentiated (papillary and follicular) and undifferentiated (anaplastic) carcinoma. Although differentiated carcinoma have relatively good prognosis, anaplastic thyroid carcinoma are highly aggressive and extremely lethal, with poor therapeutic response. External beam radiotherapy with chemotherapy would provide the chance for relative long-terrm survival of patients in thyroid anaplastic carcinoma. The discovery of new potent therapy is urgently warranted. A candidate of this strategy is gene therapy that will be selectively cytotoxic or will increase sensitivity to the ionizing radiationo for anaplastic thyroid cancer. To search the cancer-specific targets, we challenged SAGE screening (DNA Sequence 2000) and PCR-based subtraction (BBCR2001). Among the candidate genes that we found, we focused on radio-inducible hSNK gene which is transcriptionally regulated by p53 binding homology element (BBRC 2001). Next we elucidated a signal transduction pathway specifically induced by ionizing radiation in thyroid cells. It involved PKC-delta that mediates ionizing radiation-induced activation of c-Jun kinase through MKK7 (Oncogene 2001). Finally, we have demonstrated the potential gene therapy approachs in experimental model (Cancer Gene Therapy 2001, Human Gene Therapy 2000).