Thyroid Gland Anaplastic Carcinoma

P1, N=15, Recruiting, Karolinska University Hospital | Not yet recruiting --> Recruiting

P=N/A, N=560, Not yet recruiting, Chifeng Municipal Hospital; Chifeng Municipal Hospital

P2, N=60, Not yet recruiting, The First Affiliated Hospital, Sun Yat-sen University; The First Affiliated Hospital, Sun Yat-sen University

P2, N=20, Completed, Sichuan Cancer Hospital; Sichuan Cancer Hospital

PKCζ activation correlates with thyroid cancer aggressiveness and drives malignant progression through EMT regulation. ACPD effectively targets PKCζ-mediated oncogenic pathways, suggesting PKCζ inhibition as a promising therapeutic strategy for aggressive thyroid cancers.

In vivo, mice injected with tumor cells pre-cultured on high-stiffness ECM-mimicking hydrogels exhibited accelerated subcutaneous tumor growth and increased lung metastatic burden, which were significantly attenuated by FAK-targeted therapy. These findings establish ECM stiffness as a biomechanical determinant of ATC progression and metastasis, offering novel insights into microenvironment-driven malignancy and highlighting FAK as a promising therapeutic target to disrupt mechanosignaling in ATC.

These molecular insights have been incorporated into updated risk stratification frameworks, preoperative surgical planning, and treatment algorithms, informing the selection of kinase inhibitors, redifferentiation strategies, and enrollment in genotype-directed clinical trials for radioiodine-refractory disease. This review synthesizes recent evidence connecting genomic alterations to clinical behavior and highlights their translation into evolving approaches for thyroid cancer management.

Silencing FOSL1, ADAM9, or MMP9 sensitized ATC cells to NK cell-mediated cytotoxicity in vitro and suppressed ATC growth in vivo. Together, these findings highlight the role of FOSL1 in chromatin remodeling of ATC and in dampening cytotoxic functions of NK cells, thereby providing insights into the development of potential cancer therapeutics.

Notably, Fc fragment of IgG receptor IIa (FCGR2A, or CD32) was identified as a promising biomarker for ATC, implicating a functional link between immune evasion and tumor aggressiveness. Our findings provide a comprehensive molecular and immunological characterization of thyroid cancer subtypes, offering novel insights into the pathogenesis of ATC and PDTC, and identifying potential targets for diagnosis and precision therapy.

The patient began treatment with dabrafenib-trametinib, followed by pembrolizumab as second-line therapy, ultimately extending her life by nearly seven months. The complexities of accessing newer therapies in Canada's single-payer healthcare system are also emphasized. The utilization of newer rapid diagnostic technologies can have a direct impact on directing treatment for ATC and other aggressive malignancies.

The disruption of the autophagic flux leads to the accumulation of SQSTM1/p62, which in turn activates the Nrf2 pathway. In contrast to cells with functional autophagy, Nrf2-activated cells display a higher tolerance to oxidative stress, making them resistant to the senolytic activity of lysosomal inhibitors.

Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.