The expression levels of microRNA (miR)‑221‑3p and miR‑222‑3p in thyroid cancer have been found to be upregulated compared with those in normal tissues. The present study aimed to determine the effects and potential underlying mechanisms of miR‑221‑3p and miR‑222‑3p on the regulation of radioactive iodine (131I) uptake and radiosensitivity of thyroid cancer cells. The potential regulatory target genes of miR‑221‑3p and miR‑222‑3p were predicted by bioinformatics analysis, and reverse transcription‑quantitative polymerase chain reaction was used to verify miR‑221‑3p, miR‑222‑3p and target gene expression levels in thyroid cancer tissues and cell lines. Overexpression of miR‑221‑3p or miR‑222‑3p in cell models was performed using lentivirus infection. Knockdown of miR‑221‑3p and miR‑222‑3p in cells was achieved using oligonucleotide inhibitor transfection. Western blotting was used to analyze the expression levels of target proteins. In addition, the effects of miR‑221‑3p and miR‑222‑3p on the radiosensitivity of thyroid cancer cells were verified using a colony formation assay. The results of the present study revealed that the expression levels of miR‑221‑3p and miR‑222‑3p were significantly upregulated, while the expression levels of suppressor of cytokine signaling 3 (SOCS3) were downregulated in thyroid cancer tissues. Furthermore, miR‑221‑3p and miR‑222‑3p overexpression downregulated the expression levels of SOCS3, E‑cadherin and solute carrier family 5 member 5 (NIS), and upregulated the expression levels of phosphorylated STAT3 and vimentin. Following the overexpression of miR‑221‑3p or miR‑222‑3p in the FTC133 and TPC1 cell lines, their radiosensitivity was suppressed. In conclusion, the findings of the present study suggested that miR‑221‑3p and miR‑222‑3p may downregulate the expression levels of NIS and promote radioresistance. The potential mechanism was hypothesized to be associated with the miR‑221‑3p and miR‑222‑3p targeting of the SOCS3 gene, which may subsequently activate the STAT3 signaling pathway.

Purpose: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. Patients and Methods: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR–DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. Results: Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25–0.61; P < 0.0001] in Chinese patients with RAIR–DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand–foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. Conclusions: Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.

The multi-target kinase inhibitor sorafenib has been approved for the treatment of patients with advanced differentiated thyroid cancer. However, different sensitivities to sorafenib have been observed, and few patients have benefited from sorafenib treatment in the long term. In the event of acquired resistance to sorafenib it is not beneficial to continue treatment in most patients. Autophagy can be induced in a variety of cancer treatments and plays an important role in cancer treatment. The role of autophagy in sorafenib treatment of thyroid cancer has not been fully demonstrated. The present study investigated whether autophagy is activated by sorafenib during the treatment of thyroid cancer, examined the underlying mechanisms, and explored potential strategies to enhance the therapeutic sensitivity of sorafenib. Chloroquine (CQ) is an autophagy inhibitor that has been reported to increase sensitivity to various cancer treatments. Thyroid cancer xenograft model mice were treated with sorafenib, CQ, or a combination of sorafenib and CQ. We observed that CQ or sorafenib treatment suppressed tumor growth, while mice treated with the combination of sorafenib and CQ displayed significantly reduced tumor growth compared with those treated with sorafenib or CQ alone. Western blotting results indicated that sorafenib concurrently inhibited the activities of the MAPK and AKT/mTOR pathways in thyroid cancer. Autophagy was activated by sorafenib in thyroid cancer, both in vitro and in vivo, which was at least in part due to suppression of the AKT/mTOR pathway. Combination treatment including CQ could inhibit the autophagic flux induced by sorafenib. Silencing the key autophagy gene ATG5 using small interfering RNA also increased the anticancer effect of sorafenib. In summary, the present study revealed that inhibition of autophagy enhances the anticancer effect of sorafenib, and the combination of CQ with sorafenib treatment represents a potential therapeutic strategy for treating advanced differentiated thyroid cancer.

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria provide a standardized approach for assessing the nutritional status of patients and demonstrate strong predictive value for the prognosis of patients with gastric cancer. However, these criteria do not incorporate indicators of adipose tissue metabolic activity, which may reflect pro-tumor microenvironmental factors. This study investigated the combined predictive value of malnutrition, defined by the GLIM criteria, and preoperative adipose tissue ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptake for recurrence-free survival (RFS) in patients with gastric cancer following radical surgery. Methods: A total of 105 patients were retrospectively enrolled and classified into malnourished and non-malnourished groups based on the GLIM criteria. Preoperative ¹⁸F-FDG positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) was used to measure the mean standardized uptake value (SUVmean) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). The predictive values of these indicators for RFS in patients with gastric cancer were assessed. Results: Multivariate survival analysis was used to identify GLIM-defined malnutrition (p = 0.020) and increased preoperative VAT SUVmean (p = 0.042) as independent risk factors for RFS. The combined analysis revealed that patients with both malnutrition and a high preoperative VAT SUVmean had the poorest RFS (HR = 18.41, p < 0.001). The predictive model integrating GLIM criteria and VAT SUVmean outperformed the GLIM criteria alone. Conclusions: This study demonstrated that combining malnutrition defined by the GLIM criteria with preoperative visceral adipose tissue ¹⁸F-FDG uptake optimizes recurrence risk stratification and exhibits superior prognostic predictive efficacy compared to using the GLIM criteria alone. This approach provides new insights into individualized prognostic assessment and intervention strategies.