Thyroid Gland Anaplastic Carcinoma

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.

As a rate-limiting enzyme in the glycolytic pathway, pyruvate kinase M2 (PKM2), with its unique functional plasticity, has become a linchpin of glycolytic metabolism and malignant phenotypes of tumor cells. This article will systematically review the functional regulatory mechanisms of PKM2, its specific role in TC, and explore the targeted therapeutic strategies and research prospects of TC with PKM2, providing a new theoretical basis and potential plans for the clinical diagnosis and treatment.

These findings identify a NAT10/c-Myc positive feedback loop associated with tRNA ac4C modification and protein stabilization in ATC. Targeting this regulatory axis with remodelin in combination with doxorubicin may represent a promising therapeutic strategy.

Lonafarnib effectively suppresses the malignant progression of anaplastic thyroid carcinoma both in ATC cell lines and in a BALB/c nude mouse xenograft model. The mechanism involves inhibition of Ras farnesylation and the downstream ERK signaling pathway, leading to activation of Caspase-3/PARP-mediated apoptosis and GSDME-mediated pyroptosis.

We confirmed that Regorafenib disrupts this entire axis and, in combination with anti-PD-1 therapy in ATC, overcomes immunosuppression to elicit potent anti-tumor immunity. Our studies revealed the GPI/O-GlcNAcylation/THBS1 signal as a master regulator of myeloid cell crosstalk and established a novel therapeutic strategy for targeting this metabolic checkpoint to potentiate ATC immunotherapy.

Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.