Thyroid Gland Carcinoma

P=N/A, N=142, Not yet recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Apr 2029 --> Aug 2029 | Initiation date: Apr 2026 --> Aug 2026 | Trial primary completion date: Apr 2029 --> Aug 2029

P=N/A, N=150, Recruiting, Tianjin Medical University Cancer Institute and Hospital

BRAFV600E and TERT promoter co-mutation, identifiable preoperatively, defines a distinct PTC subtype with a profoundly aggressive clinicopathological profile and a significantly elevated risk of recurrence. This combined molecular signature is a potent preoperative biomarker for stratifying patients into the highest-risk category, potentially guiding more individualized initial therapeutic strategies.

Clinically, immunohistochemical evaluation of biopsy specimens demonstrated markedly lower KOR-1 expression in malignant thyroid tissues than in adjacent normal tissues. These findings reveal that Dynorphin B modulates autophagy and cytotoxicity through the mTORC1-TFE3 axis, indicating its potential to regulate thyroid cancer cell fate.

BRAF mutation is presumed to be associated with tumor progression and may predict growth of PTMC. Genetic testing including BRAF testing may help distinguishing rapid-growing thyroid cancer.

Despite I-131 treatment, she succumbed to death 6 months post-diagnosis. The index case highlights the utility of fine-needle aspiration cytology and the application of immunocytochemistry on cell blocks changing the norms for diagnosing carcinomas with an unknown primary.

Beyond their role as NIS inhibitors, perchlorate, nitrate and thiocyanate modulate oxidative stress and chemokine secretion in human thyroid cells. Thiocyanate promotes a pro-inflammatory phenotype, potentially favouring a tumour-promoting thyroid microenvironment.

Compared with the detection of either marker alone, the combined detection of Ctn and CEA improved the diagnostic accuracy for MTC but did not enhance the PPV. The combined detection also improved the predictive accuracy for cervical and lateral lymph node metastases and disease recurrence.

Resistance to RET inhibitors can be acquired through RET copy-number gain and secondary mutations as well as NF1 loss-mediated MAPK pathway activation. This mechanism of resistance can be overcome with dual inhibition of RET and downstream RAS/MAPK signaling, demonstrating clinical potential in RET-mutant MTC.

PD-L1 is a robust biomarker of aggressiveness in PTC. Integrating PD-L1 testing with molecular profiling can enhance postoperative risk stratification and guide personalized management.

Among cases with follow-up data (n=35), all 17 tumors with disease progression were DLL3 positive (13 RET-mutated tumors, 1 RAS-mutated tumor, and 3 RET/RAS wild-type tumors), including 5 with moderate expression and 12 with high expression. Most MTCs express DLL3; moreover, DLL3 expression is associated with lymph node metastases at diagnosis and disease progression, indicating that DLL3 may be an effective therapeutic target in MTC.

The present investigation suggests that tumor progression in MTC before clinical detection is a function of the time passed since tumor onset, whereas tumor onset is defined by the transformatory strength of the RET mutation. This notion, debunking the myth of immanent tumor 'aggressiveness' or "risk" imparted by RET mutations in favor of the concept of genetically encoded tumor onset, emphasizes the need for early diagnosis and intervention, ideally while tumors are still confined to the thyroid.