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Updated: Oct 1, 2026
Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
ONYX-015, an E1B gene-defective adenovirus, induces cell death in human anaplastic thyroid carcinoma cell lines
Giuseppe Portella1, Stefania Scala, Donata Vitagliano
1Department of Biology and Cellular and Molecular Pathology, Faculty of Medicine and Surgery, Federico II University of Naples, via S. Pansini 5, 80131 Naples, Italy. portella@unina.it
Abstract:
Being one of the most lethal human neoplasms and refractory to such conventional treatment as chemo- and radiotherapy, anaplastic thyroid carcinoma is a prime target for innovative therapy. p53 gene inactivation is a constant feature of this neoplasia. Therefore, we evaluated a therapeutic approach based on an E1B 55-kDa gene-defective adenovirus (ONYX-015) that replicates only in cells with impaired p53 function and leads to cell death. Here we report that the ONYX-015 virus induces cell death in three human thyroid anaplastic carcinoma cell lines (ARO, FRO, and KAT-4). In addition, we found that the growth of xenograft tumors induced in athymic mice by the injection of ARO cells was drastically reduced by ONYX-015 treatment. The ONYX-015 virus worked synergistically with two antineoplastic drugs (doxorubicin and paclitaxel) in inducing ARO and KAT-4 cell death. These results suggest that ONYX-015 may be a valid tool in the treatment of the human thyroid anaplastic carcinoma.
Insights
An innovative adenovirus therapy (ONYX-015) shows promise for anaplastic thyroid carcinoma, a lethal cancer. This virus selectively targets cancer cells with p53 gene inactivation, reducing tumor growth and enhancing chemotherapy effectiveness.
Area of Science:
- Oncolytic virotherapy
- Cancer gene therapy
- Thyroid cancer research
Background:
- Anaplastic thyroid carcinoma is a highly lethal neoplasm.
- It is often refractory to conventional chemo- and radiotherapy.
- p53 gene inactivation is a consistent characteristic of this cancer.
Purpose of the Study:
- To evaluate the therapeutic potential of an E1B 55-kDa gene-defective adenovirus (ONYX-015) for anaplastic thyroid carcinoma.
- To determine if ONYX-015 selectively targets and induces cell death in cancer cells with impaired p53 function.
- To assess the efficacy of ONYX-015 as a monotherapy and in combination with conventional chemotherapy agents.
Main Methods:
- Treatment of three human anaplastic thyroid carcinoma cell lines (ARO, FRO, KAT-4) with ONYX-015.
- Assessment of ONYX-015-induced cell death in vitro.
- Evaluation of ONYX-015 efficacy in reducing the growth of xenograft tumors in athymic mice.
- Combination studies of ONYX-015 with doxorubicin and paclitaxel.
Main Results:
- ONYX-015 effectively induced cell death in all tested anaplastic thyroid carcinoma cell lines.
- ONYX-015 treatment significantly inhibited the growth of xenograft tumors derived from ARO cells in mice.
- ONYX-015 demonstrated synergistic effects with doxorubicin and paclitaxel in inducing cancer cell death.
Conclusions:
- The E1B 55-kDa gene-defective adenovirus ONYX-015 demonstrates significant potential as a therapeutic agent for anaplastic thyroid carcinoma.
- ONYX-015 exhibits selective toxicity towards cancer cells with p53 inactivation.
- This oncolytic virus may serve as a valuable addition to treatment strategies for anaplastic thyroid carcinoma, potentially enhancing the efficacy of existing therapies.
