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

xlomafota13 shared this article with you from Inoreader Targeting the mTOR Pathway in Hurthle Cell Carcinoma Results in Potent Anti-Tumor Activity Via radioactive iodine Mol Cancer Ther. 2021 Nov 17:molcanther.0224.2021. doi: 10.1158/1535-7163.MCT-21-0224. Online ahead of print. 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 detaile d 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. PMID:34789562 | DOI:10.1158/1535-7163.MCT-21-0224 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.