Thyroid Gland Anaplastic Carcinoma

We describe a patient with radioactive iodine-refractory, metastatic oncocytic thyroid carcinoma with an NBN gene (c.2166_2167delGCinsAT) pathogenic variant, who developed progressive disease despite receiving systemic therapy with lenvatinib and pembrolizumab. A mutual exclusivity analysis demonstrated a tendency for pathogenic variants in one MRN complex genes to co-occur with pathogenic variants in the other two MRN complex genes. In conclusion, the MRN complex pathogenic variants could be potentially oncogenic in TCs and may be linked to aggressive forms of TC.

Pin1 knockdown or treatment with the pharmacological Pin1 inhibitor KPT-6566 stabilizes NCOA4, enhances ferritinophagy, and triggers ferroptosis, markedly restraining ATC growth both in vitro and in vivo. These findings identify Pin1 as a previously unrecognized suppressor of ferroptosis through NCOA4-dependent ferritinophagy and support Pin1 inhibition as a potential therapeutic strategy for ATC.

This study validated the hypothesis that Trp53 deletion and Braf mutation promote the progression of PTC to ATC through ultrasound monitoring and computer modeling. Certain PTCs with the potential for dedifferentiation exhibit a specific molecular expression profile, which may represent potential therapeutic targets.

This study elucidates the molecular mechanism by which HIF-1α mediates anti-ferroptosis in ATC through regulating lipid metabolism and proposes a promising therapeutic strategy in which HIF-1α inhibition acts synergistically with PD-1 blockade for the treatment of ATC.

Future efforts should focus on combination therapies, biomarker-driven patient stratification, and the development of targeted delivery systems to overcome toxicity and resistance. A deeper understanding of tumor metabolic heterogeneity will be essential for translating these approaches into clinical practice.

P2, N=27, Active, not recruiting, Hospices Civils de Lyon | Recruiting --> Active, not recruiting | N=154 --> 27

These findings suggest that delivering vemurafenib in polymeric nanocapsules produces delayed but sustained cytotoxic and apoptotic effects in ATC cells in vitro, warranting further investigation of this nanocarrier approach for thyroid cancer treatment. Altogether, the biological results reported in this study are derived from in vitro experiments and require further validation in in vivo models.

BRAFV600E-mutant ATC displays distinct clinical features and improved survival when treated with targeted therapy; ddPCR-based liquid biopsy provides a rapid and sensitive method for BRAFV600E detection and may support timely therapeutic decision-making. Serial LB analysis may contribute to disease monitoring and detection of resistance mechanisms in selected patients.

Although paclitaxel and lenvatinib have been used as drug treatments, combination therapy with dabrafenib and trametinib has recently been reported to be effective. Furthermore, lenvatinib, a molecularly targeted agent, shows limited efficacy against ATC and is associated with frequent adverse events. In contrast, combination therapy with dabrafenib and trametinib is considered an effective therapeutic option for patients with BRAF V600E mutation-positive ATC, when appropriate management and monitoring are implemented.

In vivo, Dendrobine reduced tumor volume and weight (P < 0.001), decreased IL-6 content in tumors (P < 0.05), improved liver function indices by reducing AST, ALT and ALP activities (P < 0.05), and exhibited no nephrotoxic effects. Dendrobine exerts antitumor effects in ATC by targeting the JAK-STAT3 pathway, providing a promising therapeutic candidate.

Due to high PD-L1 expression of the tumor, the patient was offered off-label immunotherapy with an immune checkpoint inhibitor (ICI) (nivolumab monotherapy) and demonstrated a remarkable radiographic and clinical response, achieving prolonged progression-free survival (12 months) and overall survival (18 months). ICIs may represent a valuable therapeutic option for patients with metastatic ATC exhibiting high PD-L1 expression. The presented case report and literature review underscore the need for clinical trials to confirm the efficacy of immunotherapy in ATC.

TTK expression is markedly upregulated in highly malignant ATC tissues compared to benign lesions and PTC. The protein level of TTK emerges as a valuable diagnostic marker for distinguishing between benign and malignant thyroid conditions and serves as a crucial prognostic indicator for ATC. Further exploration and validation of its application in clinical practice are warranted.