Conclusions
I here summarized the recent articles regarding gene therapy for thyroid cancer. Although there have been tremendous progresses in this field in the last decade, there is unfortunately no published report on clinical trial of gene therapy for thyroid cancer [except one patient treated with ONYX-015 (66)]. Patients with thyroid cancer, particularly those with anaplastic and medullary cancers, will hopefully benefit from gene therapy approach in the near future.
Keywords
- Thyroid Cancer
- Thyroid Carcinoma
- Medullary Thyroid Carcinoma
- Medullary Thyroid Cancer
- Thyroid Cancer Cell
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Roth J.A., Cristiano R.J. Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 1997; 89: 21–39.
Fagin J.A. Perspective: lesson learned from molecular genetic studies of thyroid cancer-insights into pathogenesis and tumor-specific therapeutic targets. Endocrinology 2002; 143: 2025–2028.
Scala S., Portella G., Fedele M., Chiappetta G., Fusco A. Adenovirus-mediated suppression of HMG(Y) protein synthesis as potential therapy of human malignant neoplasias. Proc Natl Acad Sci USA 2000; 97: 4256–4261.
Cerutti J., Trapasso F., Battaglia C., Zhang L., Martelli M.L., Visconti R., Berlingieri M.T., Fagin J.A., Santoro M., Fusco A. Block of c-myc expression by antisense oligonucleotides inhibits proliferation of human thyroid carcinoma cell lines. Clin Cancer Res 1996; 2:119–126.
Levine A.J. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323–331.
Fagin J.A., Matsuo K., Karmakar A., Chen D.L., Tang S.H., Koeffler H.P. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest 1993; 91: 179–184.
Donghi R., Longoni A., Pilotti S., Michieri P., Porta G.D., Pierotti M.A. Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland. J Clin Invest 1993; 91: 1753–1760.
Ito T., Seyama T., Mizuno T., Tsuyama N., Hayashi T., Hayashi Y., Dohi K., Nakamura N., Akiyama M. Unique association of p53 mutations with undifferentiated but not differentiated carcinomas of the thyroid. Cancer Res 1992; 52: 1369–1371.
Battista S., Martelli S., Fedele M., Chiappetta G., Trapasso F., De Vita G., Battaglia C., Santoro M., Viglietto G., Fagin J.A. A mutated p53 gene alters thyroid cell differentiation. Oncogene 1995; 16: 2029–2037.
Fagin J.A., Tang S.H., Zeki K., Lauro R., Fusco A., Gonsky R. Reexpression of thyroid peroxidase in a derivative of an undifferentiated thyroid carcinoma cell line by introduction of wild-type p53. Cancer Res 1996; 56: 765–771.
Morreti F, Farsetti A., Soddu S., Misiti S., Crescenzi M., Filetti S., Andreoli M., Sacchi A., Pontecorvi A. p53 re-expression inhibits proliferation and restores differentiation of human thyroid anaplastic carcinoma cells. Oncogene 1997; 14: 729–740.
Yang T.-T., Namba H., Hara T., Takamura N., Nagayama Y., Fukata S., Ishikawa N., Kuma K., Ito K., Yamashita S. p53 induced by ionizing radiation mediates DNA end-jointing activity, but not apoptosis of thyroid cells. Oncogene 1997; 14: 1511–1519.
Velasco J.A., Medina D.L., Romero J., Mato M.E., Santisteban P. Introduction of p53 induces cell-cycle arrest in p53-deficient human medullary thyroid-carcinoma cells. Int J Cancer 1997; 73: 449–455.
Kim S.-B., Ahn I.-M., Park H.-J., Park J.-S., Cho H.-J., Gong G., Suh C., Lee J.-S., Kim W.-K., Kim S.-H. Growth inhibition and chemosensitivity of poorly differentiated human thyroid cancer cell line (NPA) transfected with p53 gene. Head & Neck 2001; 23: 223–229.
Narimatsu M., Nagayama Y., Akino K., Yasuda M., Yamamoto T., Yang T.-T., Ohtsuru A., Namba H., Ayabe H., Yamashita S., Niwa M. Therapeutic usefulness of wild-type p53 gene introduction in a p53-null anaplastic thyroid carcinoma cell line. J Clin Endocrinol Metab 1998; 83: 3668–3672.
Nagayama Y., Shigematsu K., Namba H., Zeki K., Yamashita S., Niwa M. Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by p53 in a p53-null thyroid carcinoma cell line in vivo. Anticancer Res 2000; 20: 2723–2728.
Blagosklonny M.V., Giannakakou P., Wojtowicz M., Romanova L.Y., Ain K.B., Bates S.E., Fojo T. Effects of p53-expressing adenovirus on the chemosensitivity and differentiation of anaplastic thyroid cancer cells. J Clin Endocrinol Metab 1998; 83: 2516–2522.
Nagayama Y., Yokoi H., Takeda K., Hasegawa M., Nishihara E., Namba H., Yamashina S., Niwa M. Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo. J Clin Endocrinol Metab 2000; 85: 4081–4086.
Imanishi R., Ohtsuru A., Iwamatsu M., Lioka T., Namba H., Seto S., Yano K., Yamashita S. A histone deacetylase inhibitor enhances killing of undifferentiated thyroid carcinoma cells by p53 gene therapy. J Clin Endocrinol Metab 2002; 87: 4821–4824.
Davis B.M., Koc O.N., Lee k., Gerson S.L. Current progress in the gene therapy of cancer. Cur Opin Oncol 1996; 8: 499–508.
Nishihara E., Nagayama Y., Watanabe M., Narimatsu M., Namba H., Niwa M., Yamashita S. Treatment of thyroid carcinoma cells with four different suicide gene/prodrug combinations in vitro. Anticancer Res 1998; 18: 1521–1526.
Nishihara E., Nagayama Y., Mawatari F., Tanaka K., Naniba H., Niwa M., Yamashita S. Retrovirus-mediated herpes simplex virus thymidine kinase gene transduction renders human thyroid carcinoma cell lines sensitive to ganciclovir and radiation in vitro and in vivo. Endocrinology 1997; 138: 4577–4583.
van der Eb M.M., Cramer S.J., Vergouwe Y, Schagen F.H., van Krieken J.H., van der Eb A.J., Rinkers I.H., van de Velde C.J., Hoeben R.C. Severe hepatic dysfunction after adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration. Gene Ther 1998; 5: 451–458.
Wallace H., Ledent C., Vassart G., Bishop J.O., Al-Shawi R. Specific ablation of thyroid follicle cells in adult transgenic mice. Endocrinology 1991; 129: 3217–3226.
Zeiger M., Takiyama Y., Bishop J.O., Ellison A.R., Saji M., Levine M.A. Adenoviral infection of thyroid cells: a rationale for gene therapy for metastatic thyroid carcinoma. Surgery 1996; 120: 921–925.
Braiden V, Nagayama Y, Iitaka M., Namba H., Niwa M., Yamashita S. Retrovirus-mediated suicide gene/prodrug therapy targeting thyroid carcinoma using a thyroid-specific promoter. Endocrinology 1998; 139: 3996–3999.
Zhang R., Straus F, DeGroot L.J. Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity. Thyroid 2001; 11: 115–123.
Zhang R., Straus F.H., DeGroot L.J. Cell-specific viral gene therapy of a Hurthle cell tumor. J Clin Endocrinol Metab 2002; 87:1407–14.
Nagayama Y, Nishihara E., Iitaka M., Namba H., Yamashita S., Niwa M. Enhanced efficacy of tran-scriptionally targeted suicide gene/prodrug therapy for thyroid carcinoma with the Cre-loxP system. Cancer Res 1999 59: 3049–3052.
Takeda T., Yamazaki M., Minemura K., Imai Y, Inaba H., Suzuki S., Miyamoto T., Ichikawa K., Kakizawa T., Mori J., DeGroot L.J., Hashizume K. A tandemly repeated thyroglobulin core promoter has potential to enhance efficacy for tissue-specific gene therapy for thyroid carcinoma. Cancer Gene Ther 2002; 9: 864–874.
Chun Y.S., Saji M., Zeiger M.A. Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines. Surgery 1998; 124: 1100–1105.
Shimura H., Suzuki H., Miyazaki A., Furuya F, Ohta K., Haraguchi K., Endo T, Onaya T. Transcriptional activation of the thyroglobulin promoter directing suicide gene expression by thyroid transcription factor-1 in thyroid cancer cells. Cancer Res 2001; 61: 3640–3646.
Kitazono M., Chuman Y, Aikou T., Fojo T. Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone dcacetylase inhibitors and agents modulating the cyclic adenosine 3’,5’-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells. J Clin Endocrinol Metab 2001; 86: 834–840.
Kitazono M., Chuman Y, Aikou T., Fojo T. Adenovirus HSV-TK construct with thyroid-specific promoter: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cAMP pathway. Int J Cancer 2002; 99: 453–459.
Zhang R., DeGroot L.J. Gene therapy of established medullary thyroid carcinoma with herpes simplex viral thymidine kinase in a rat tumor model: relationship of bystander effect and antitumor efficacy. Thyroid 2000; 10: 313–319.
Minemura K. Takeda T., Minemura K., Nagasawa T., Zhang R., Leopardi R., DeGroot L.J. Cell-specific induction of sensitivity to ganciclovir in medullary thyroid carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase. Endocrinology 2000; 1814–1822.
Soler M.N., Bobe P., Benohoud K., Lemaire G., Roos A., Lausson S. Gene therapy of rat medullary thyroid cancer by naked nitric oxide synthase II DNA injection. J Gene Med 2000; 2: 344–352.
Lausson S., Fournes B., Borrel C., Milhaud G., Treilhou-Lahille F. Immune response against medullary thyroid carcinoma induced by parental and/or interleukin-2-secreting MTC cells in a rat model of human familial MTC. Cancer Immunol Immunother 1996; 43: 116–123.
Zhang R., Baunoch D., DeGroot L.J. Genetic immunotherapy for medullary thyroid carcinoma: destruction of tumors in mice by in vivo delivery of adenovirus vector transducing the murine interleukin-2 gene. Thyroid 1998; 8: 1137–11464.
Zhang R., Minemura K., DeGroot L.J. Immunotherapy for medullary thyroid carcinoma by a replication-defective adenovirus transducing murine IL-2. Endocrinology 1998; 139: 601–608.
Zhang R., Straus F.H., DeGroot L.J. Effective genetic therapy of established medullary thyroid carcinomas with murine interleukin-2: dissemination and cytotoxicity studies in a rat model. Endocrinology 1999; 140: 2152–2158.
Zhang R., DeGroot L.J. Genetic immunotherapy of established tumours with adenovirus vectors transducing murine interleukin-12 subunits in a rat medullary thyroid carcinoma model. Clin Endocrinol 2000; 52: 687–694.
Yamazaki M., Zhang R., Straus F.H., Messina M., Robinson B.G., Hashizume K. DeGroot L.J. Effective gene therapy for medullary thyroid carcinoma using recombinant adenovirus inducing tumor-specific expression of interleukin-12. Gene Therapy 2002; 9: 64–74.
Zhang R., DeGroot L.J. Gene therapy of a rat follicular thyroid carcinoma model with adenoviral vectors transducing murine interleukin-12. Endocrinology 2003; 144:1393–8.
Soler M.N., Milhaud G., Lekmine F., Treilhou-Lahille F., Klatzmann D., Lausson S. Treatment of medullary thyroid carcinoma by combined expression of suicide and interleukin-2 genes. Cancer Immunol Immunother 1999; 48: 91–99.
Zhang R., DeGroot L.J. An adenoviral vector expressing functional heterologous proteins herpes simplex viral thymidine kinase and human interleukin-2 has enhanced in vivo antitumor activity against medullar thyroid carcinoma. Endocr Relat Cancer 2001; 8: 315–325.
Barzon L., Bonaguro R., Castagliuolo I., Chilosi M., Franchin E., Del Vecchio C., Giaretta I., Boscaro M., Palu G. Gene therapy of thyroid cancer via retrovirally-driven combined expression of human interleukin-2 and herpes simplex virus thymidine kinase. Eur J Endocrinol 2003; 148: 73–80.
Haupt K., Siegel F., Lu M., Yang D., Hilken G., Mann K., Roggendorf M., Sailer B. Induction of a cellular and humoral immune response against preprocalcitonin by genetic immunization: a potential new treatment for medullary thyroid carcinomas. Endocrinology 2001; 142: 1017–1023.
Heise C., Kirn D.H. Replication-selective adenoviruses as oncolytic agents. J Clin Invest 2000; 105: 847–851.
Bischoff J.R., Kirn D.H., Willimas A., Heise C., Horn S., Muna M., Ng L., Nye J.A., Sampson-Johannes A., Fattaey A., McCormick F. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996; 274: 373–376.
Portella G., Scala S., Vitagliano D., Vecchio G., Fusco A. ONYX-015, an E1B gene-defective adenovirus, induces cell death in human anaplastic thyroid carcinoma cell lines. J Clin Endocrinol Metab 2002; 87: 2525–2531.
Nagayama Y, Nishihara E., Namba H., Yokoi H., Hasegawa M., Mizuguchi H., Hayakawa T, Yamashita S., Niwa M. Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre-loxP system. Cancer Gene Ther 2001; 8: 36–44.
Prabakaran I., Kesmodel S.B., Menon C., Molnar-Kimber K., Fraker D.L. A replication-selective adenoviral vector driven by the human Tg promoter-enhancer is selective for Tg+ thyroid cancer cells. Abstract for 93rd Annual Meeting of American Association for Cancer Research 2002;43: #3782.
Hermiston T.W, Kuhn I. Armed therapeutic viruses: strategies and challenges to arming oncolytic viruses with therapeutic genes. Cancer Gene Ther 2002; 9: 1022–1035.
Kong H.-L., Crystal R.G. Gene therapy strategies for tumor antiangiogenesis. J Natl Cancer Inst 1998; 90: 273–286.
Dai G., Levy O., Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature 1996; 379: 458–460.
Scott V.C., Wang R., Kreman T.M., Sheffield V.C., Karnishki L.P. The Pendred syndrome gene encodes a chloride-iodide transporter. Nat Genet 1999; 21: 440–443.
Spitzweg C., Harrington K.J., Pinke L.A., Vile R.G., Morris J.C. The sodium iodide symporter and its potential role in cancer therapy. J Clin Endocrinol Metab 2001; 86: 3327–3335.
Heufelder A.E., Morgenthaler N., Schipper M.L., Joba W. Sodium iodide symporter-based strategies for diagnosis and treatment of thyroid and nonthyroid malignancies. Thyroid 2001; 11: 839–847.
Shimura H., Haraguchi K., Miyazaki A., Endo T, Onaya T. Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I- symporter gene. Endocrinology 1997; 138: 4493–4496.
Spitzweg C., O’Connor M.K., Bergert E.R., Tindall D.J., Young C.Y.F., Morris J.C. Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Res 2000; 60: 6526–6530.
Cho J.-Y, Shen D.H.Y., Yang W., Williams B., Buckwalter T.L.F., La Perle K.M.D., Hinkle G., Pozderac R., Kloos R., Nagaraja H.N., Barth R.F., Jhiang S.M. In vivo imaging and radioiodide therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas. Gene Ther 2002; 9:1139–1145.
Huang M., Batra R.K., Kogai T., Lin Y.Q., Hershman J.M., Lichtenstein A., Sharma S., Zhu L.X., Brent G.A., Dubinett S.M. Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non-small cell lung cancer. Cancer Gene Ther 2001; 8: 612–618.
Zarnegar R., Brunaud L., Kanauchi H., Wong M., Fung M., Ginzinger D., Duh Q.Y., Clark O.H. Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor. Surgery 2002; 132: 984–90.
Tazebay U.H., Wapnir I.L., Levy O., Dohan O., Zuckier L.S., Hhua Zhao Q., Fu Deng H., Amenta P.S., Fineberg S., Pestell R.G., Carrasco N. The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med 2000; 6: 871–878.
Nemunaitis J., Cunningham C., Buchanan A., Blackburn A., Edelman G., Maples P., Netto G., Tong A., Randlev B., Olson S., Kirn D. Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity. Gene Ther 2001; 8: 746–759.
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Nagayama, Y. (2005). Gene Therapy for Thyroid Cancer. In: Farid, N.R. (eds) Molecular Basis of Thyroid Cancer. Cancer Treatment and Research, vol 122. Springer, Boston, MA. https://doi.org/10.1007/1-4020-8107-3_21
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