The mixed expression of BRAF under varying levels of differentiation may explain, in part, the contradictory studies regarding the impact of BRAF mutations on patient prognosis and also indicates a complex genomic signature for dedifferentiated thyroid cancer.
Although most of the US Food and Drug Administration (FDA)-approved drugs are antiangiogenic multikinase inhibitors-vandetanib, cabozantinib, sorafenib, lenvatinib-there are two FDA indications that are mutation specific-dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer.
This includes frequently reported gene fusions such as CCDC6/RET (PTC1), PRKAR1A/RET (PTC2) and ETV6/NTRK3 , and gene fusions that are less common in thyroid cancer (TPM3/NTRK1, EML4/ALK and EML4/NTRK3).
We further demonstrate that upfront combined inhibition of FAK and Src synergistically inhibits growth and invasion, and induces apoptosis in a panel of BRAF- and RAS-mutant thyroid cancer cell lines.
Furthermore, glycolysis-related enzymes, such as LDHA and PKM2, were upregulated in BRAFV600E mutant thyroid cancer specimens, thereby promoting glycolysis.
Combination strategies involving immune checkpoint inhibitors (ICIs) with tyrosine kinase (TK) or serine/threonine protein kinase B-raf (BRAF) inhibitors are showing considerable promise in the treatment of advanced thyroid cancer.
Hence, recent research efforts have been performed trying to explore several inhibitors of the V600E mutation-containing BRAF kinase as potential therapeutic options in thyroid cancer refractory to standard interventions.
In conclusion, the results of the current study suggest that BRAF<sup>V600E</sup>-induced KRT19 expression may promote thyroid cancer metastasis via EMT.
Several drugs targeting RET have been approved by the FDA for the treatment of cancer: (i) cabozantinib and vandetanib for medullary thyroid carcinomas and (ii) lenvatinib and sorafenib for differentiated thyroid cancers.
In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC.
Our results demonstrate a strong clinical potential for the combination of the Bortezomib and the BRAF inhibitor Vemurafenib as an efficient therapeutic approach for the treatment of TC.
Therefore, we examined the efficacy of the combination therapy across a panel of thyroid cancer cell lines representing common oncogenic drivers (BRAF, RAS, and PIK3CA).
This study explores the possibility of building AI models without precise pixel-level annotation in prediction of the tumor size, extrathyroidal extension, lymph node metastasis, cancer stage and BRAF mutation in thyroid cancer diagnosis, providing the patients' background information, histopathological and immunohistochemical tissue images.
Several multikinase inhibitors with activity against RET have been explored in the clinic, and confirmed responses to targeted therapy with these agents have been observed in patients with RET-rearranged lung cancers or RET-mutant thyroid cancers.
These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression.
Unusually long-term responses to vemurafenib in BRAFV600E mutated colon and thyroid cancers followed by the development of rare RAS activating mutations.