In this phase 2, multicentre, non-randomised, open-label study, we enrolled adult patients (aged ≥18 years) with pretreated metastatic stage IV BRAF(V600E)-mutant NSCLC who had documented tumour progression after at least one previous platinum-based chemotherapy and had had no more than three previous systemic anticancer therapies.
Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression.
RAS/BRAF mutations of colorectal cancer (CRC) play a crucial role in carcinogenesis and cancer progression and need to be considered for the therapeutic strategy choice.
The aim of this study was to genotype a series of papillary thyroid carcinomas (PTCs) and anaplastic thyroid carcinomas (ATCs) for BRAF mutation, and to evaluate p53 and SOX2 expression as factors implicated in tumour progression.
Beyond development, we can look into the effectiveness of already approved targeted therapies (eg, anti-BRAF(V600E) selective inhibitors, tyrosine kinase inhibitors, histone deacetylase inhibitors, inhibitors of DNA methylation, etc) to potentially test in ATC after learning the molecular mechanisms that aid in tumor progression.
In summary, these results suggest that activating B-Raf mutations initially promote nevi development, but the resulting high, intense activation of the MAPK pathway inhibits further tumor progression requiring Akt3 activation to bypass this barrier and aid melanoma development.
We also used BRAF(V637E) knock-in mice to follow changes in the stem cell pool during serrated tumor progression and found ISC marker expression reduced in serrated hyperplasia forming after BRAF activation, but intensified in progressive dysplastic foci characterized by additional mutations that activate the Wnt/β-catenin pathway.
Somatic mutations of BRAF and NRAS oncogenes are thought to be among the first steps in melanoma initiation, but these mutations alone are insufficient to cause tumor progression.
To determine the role of mutations in BRAF and KRAS2 in the neoplastic progression of Barrett's adenocarcinoma, we analysed both genes for common mutations.
The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases.
It is assumed that BRAF(V600E) may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.
Thirty-seven tumor biopsies were collected from 15 patients with unresectable American Joint Committee on Cancer stage III or IV melanoma immediately before and approximately 7 days after the commencement of BRAF inhibitor treatment and at the time of tumor progression.
The observation of TERT promotor and BRAF mutations in sporadic MPNSTs and the absence of TERT promotor and rarity of BRAF mutations in NF1 related tumors may imply an alternative genetic route of tumor progression in both patient groups.
In summary, we showed that PLGG tumorigenicity was low despite the presence of putative CSCs, and our data supported GFAP<sup>-</sup>/Vimentin<sup>+</sup> cells, <i>CDKN2A</i> homozygous deletion in trisomy chromosome 9 cells, and <i>BRAF V600E</i> mutation as candidate drivers of tumor progression in the PXA xenografts.
Despite compelling initial RRs, development of treatment resistance eventually leads to tumor progression in the majority of BRAF/MEK-inhibitor treated patients.
Many melanomas harbor a mutation in this pathway, BRAF(V600E), which constitutively activates MAPK signaling and expression of downstream target genes that facilitate tumor progression.
BRAF mutation leads to a constitutive activation of mitogen activated protein kinase pathway which is essential for cell proliferation and tumor progression.
Using gene set enrichment analysis and in vitro and in vivo functional studies, we identified and validated a B-Raf(V600E) gene set signature associated with tumor progression in PTCs.
One of our patients had a rare activating BRAF mutation detected through tumor exome sequencing, which led to a switch from her successful therapy to Vemurafenib and ultimately tumor progression.