We tested the effects of a highly selective B-Raf(V600E) inhibitor, PLX4720, on proliferation, migration, and invasion both in human thyroid cancer cell lines (8505c(B-RafV600E) and TPC-1(RET/PTC-1 and wild-type B-Raf)) and in primary human normal thyroid (NT) follicular cells engineered with or without B-Raf(V600E).
The molecular pathology of thyroid cancer is now better understood because of our ability to identify RET/PTC rearrangements and BRAF mutations in the aetiopathogenesis of the large majority of PTCs and the high prevalence of RAS mutations and PAX8/PPARgamma rearrangements in follicular patterned carcinomas (FTCs and follicular variant of PTCs).
The objectives of the study were: 1) to determine the prevalence of TERT promoter mutations C228T and C250T in different thyroid cancer histological types and cell lines; and 2) to establish the possible association of TERT mutations with mutations of BRAF, RAS, or RET/PTC.
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.
These results reveal a novel (V600E)BRAF-induced mechanism in thyroid tumours progression and provides a rationale for using the PLX4720 inhibitor to target (V600E)BRAF signalling to effectively control progression of thyroid cancer.
BRAF(V600E) mutation analysis is superior to RAS point mutations and evaluation of RET/PTC rearrangements in the diagnosis of thyroid cancer, even in indeterminate lesions.
We tested the effects of a highly selective B-Raf(V600E) inhibitor, PLX4720, on proliferation, migration, and invasion both in human thyroid cancer cell lines (8505c(B-RafV600E) and TPC-1(RET/PTC-1 and wild-type B-Raf)) and in primary human normal thyroid (NT) follicular cells engineered with or without B-Raf(V600E).
Mutation detection in samples from thyroid cancer with the addition of BRAF mutation, and also the detection of RAS, RET/PTC, and PAX8/PPARγ mutations, may also contribute to cancer diagnosis.
Common somatic mutations in BRAF, rearranged in transformation/papillary thyroid carcinomas (RET/PTC) and neurotrophin receptor-tyrosine kinase (NTRK) also do not account for the gender disparity in thyroid cancer.
BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in 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.
High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.
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.
Acquired resistance to BRAF inhibition induces epithelial-to-mesenchymal transition in BRAF (V600E) mutant thyroid cancer by c-Met-mediated AKT activation.
Furthermore, glycolysis-related enzymes, such as LDHA and PKM2, were upregulated in BRAFV600E mutant thyroid cancer specimens, thereby promoting glycolysis.
In this work, we attempt to discuss some of the most recent molecular, preclinical and clinical evidence to construct a more exhaustive model of function for the BRAFV600E in development, progression and therapeutic approach of thyroid cancer.
Unusually long-term responses to vemurafenib in BRAFV600E mutated colon and thyroid cancers followed by the development of rare RAS activating mutations.