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ONYX-015 Enhances Radiation-Induced Death of Human Anaplastic Thyroid Carcinoma Cells

Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.P., S.L., G.V., A.F.), Università di Napoli Federico II, Istituto di Biostrutture e Bioimmagini Consiglio Nazionale delle Ricerche (R.P., L.C.), and Dipartimento di Diagnostica per Immagini e Radioterapia (M.S.), Università di Napoli Federico II, 80131 Naples

Address all correspondence and requests for reprints to: Giuseppe Portella, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli Federico II, via S. Pansini 5, 80131 Napoli, Italy. E-mail: portella{at}unina.it.

ONYX-015 is a genetically modified adenovirus with a deletion of the E1B early gene and therefore is designed to replicate preferentially in p53-mutated cells causing their death. We previously demonstrated that the ONYX-015 virus kills anaplastic thyroid carcinoma (ATC) cells and enhances the antineoplastic effects of doxorubicin and paclitaxel. Here we report that ONYX-015 increased the cytopathic effect of radiotherapy in three ATC cell lines. In fact, ONYX-015 and radiation induced a significant cytopathic effect on ATC cells. DNA fragmentation analysis showed that ATC ONYX-015-treated cells were very sensitive to radiation-induced apoptosis. In addition, low doses of ONYX-015 associated with a single radiation dose of 10 Gy delayed the growth of a xenograft tumor induced by ARO cells in athymic mice. Our results suggest that the combination of ONYX-015 and radiotherapy should be considered for experimental trials in patients with anaplastic thyroid carcinoma.

This study was supported by the Associazione Italiana per la Ricerca sul Cancro, by the Programa Italia-USA sulla Terapia dei Tumori coordinated by Prof. C. Peschle.

Abbreviations: ATC, Anaplastic thyroid carcinoma; CMV, cytomegalovirus; MOI, multiplicity of infection; pfu, plaque-forming units.

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