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Dong Y, Gong Y, Kuo F, et al. Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Anti-Tumor Activity. Mol Cancer Ther. 2021;doi: 10.1158/1535-7163.MCT-21-0224.
Dong, Y., Gong, Y., Kuo, F., Makarov, V., Reznik, E., Nanjangud, G. J., Aras, O., Zhao, H., Qu, R., Fagin, J. A., Sherman, E. J., Xu, B., Ghossein, R., Chan, T. A., & Ganly, I. (2021). Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Anti-Tumor Activity. Molecular cancer therapeutics, . https://doi.org/10.1158/1535-7163.MCT-21-0224
Dong, Yiyu, et al. "Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Anti-Tumor Activity." Molecular cancer therapeutics vol. (2021). doi: https://doi.org/10.1158/1535-7163.MCT-21-0224
Dong Y, Gong Y, Kuo F, Makarov V, Reznik E, Nanjangud GJ, Aras O, Zhao H, Qu R, Fagin JA, Sherman EJ, Xu B, Ghossein R, Chan TA, Ganly I. Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Anti-Tumor Activity. Mol Cancer Ther. 2021 Nov 17; doi: 10.1158/1535-7163.MCT-21-0224. Epub 2021 Nov 17. PMID: 34789562.
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Mol Cancer Ther. 2021 Nov 17; doi: 10.1158/1535-7163.MCT-21-0224. Epub 2021 Nov 17.

Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Anti-Tumor Activity.

Molecular cancer therapeutics

Yiyu Dong, Yongxing Gong, Fengshen Kuo, Vladimir Makarov, Ed Reznik, Gouri J Nanjangud, Omer Aras, HuiYong Zhao, Rui Qu, James A Fagin, Eric J Sherman, Bin Xu, Ronald Ghossein, Timothy A Chan, Ian Ganly

Affiliations

  1. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center.
  2. Center for immunotherapy, Cleveland Clinic.
  3. Immunogenomics & Precision Oncology Platform, Memorial Sloan Kettering Cancer Center.
  4. CITI, Memorial Sloan Kettering Cancer Center.
  5. Computational Oncology, Memorial Sloan Kettering Cancer Center.
  6. Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center.
  7. Radiology, Memorial Sloan Kettering Cancer Center.
  8. Anti-tumor assessment facility, Memorial Sloan Kettering Cancer Center.
  9. Medical Oncology, Memorial Sloan Kettering Cancer Center.
  10. Pathology, Memorial Sloan Kettering Cancer Center.
  11. Center for Immunotherapy, Cleveland Clinic.
  12. Head and Neck Surgery, Memorial Sloan Kettering Cancer Center [email protected].

PMID: 34789562 DOI: 10.1158/1535-7163.MCT-21-0224

Abstract

Hurthle cell carcinomas (HCC) are refractory to radioactive iodine and unresponsive to chemotherapeutic agents, with a fatality rate that is the highest among all types of thyroid cancer after anaplastic thyroid cancer. Our previous study on the genomic landscape of HCCs identified a high incidence of disruptions of mTOR pathway effectors. Here, we report a detailed analysis of mTOR signaling in cell line and patient-derived xenograft (PDX) mouse models of HCCs. We show that mTOR signaling is upregulated and that targeting mTOR signaling using mTOR inhibitors suppresses tumor growth in primary tumors and distant metastasis. Mechanistically, ablation of mTOR signaling impaired the expression of p-S6 and cyclin A2, resulting in the decrease of S phase and blocking of cancer cell proliferation. Strikingly, mTOR inhibitor treatment significantly reduced lung metastatic lesions, with the decreased expression of Snail in xenograft tumors. Our data demonstrates that mTOR pathway blockade represents a novel treatment strategy for HCC.

Copyright ©2021, American Association for Cancer Research.

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