The EGFR-KRAS-BRAF-MEK-ERK (MAPK) pathway plays an important role in most cancers with close association of EGFR, KRAS or BRAF mutations with carcinogenesis and drug resistance. EGFR have been developed for molecular targeted therapy of various cancers. However, it remains to be determined whether aberration of this pathway is essential for the survival of clear cell renal cell carcinoma (CCRCC...

PURPOSE Certain clinicopathologic features correlate with BRAF mutation status in melanoma including younger age and primary subtype. This study sought to determine the BRAF mutation status by age-decade and whether BRAF-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma. METHODS A prospectively assembled cohort of Australian patients ...

Various types of human cancers harbor BRAF somatic mutations, leading researchers to seek molecular targets for BRAF inhibitors. A mutually exclusive relationship has been observed between the BRAF-V600E mutation and K-ras mutations, suggesting that the BRAF-V600E mutation may differ from the other BRAF mutant types. Here, we used microarray analysis to examine differences between the BRAF and ...

Oncogenic mutations in the BRAF gene are detected in approximately 7% of human cancer samples with a particularly high frequency of mutation in malignant melanomas. Over 40 different missense BRAF mutations have been found, but the vast majority (>90%) represent a single nucleotide change resulting in a valine-->glutamate mutation at residue 600 ((V600E)BRAF). In cells cultured in vitro, (V600E...

BRAF inhibitor monotherapy appears to be ineffective in BRAF (V600E)-positive colorectal cancer (CRC) as a result of inherent EGFR-mediated resistance mechanisms. This concept initiated combinatorial treatment approaches. Nevertheless, BRAF inhibition in isogenic CRC cell lines induced enhanced cell-cell adhesion and differentiation, underlining a potential benefit of BRAF inhibitors in CRC.

Here, we applied optoRAF, an optogenetic tool for light-controlled clustering and activation of RAF proteins that mimics the natural occurring RAS-mediated dimerization. This versatile tool allows studying the effect on BRAF and CRAF homodimer- as well as heterodimer-induced RAF signaling. Vemurafenib and dabrafenib are two clinically approved inhibitors for BRAF that efficiently suppress the k...

Langerhans cell histiocytosis (LCH) represents a clonal proliferation of Langerhans cells. BRAF V600E mutations have been identified in approximately 50% of cases. To discover other genetic mechanisms underlying LCH pathogenesis, we studied 8 cases of LCH using a targeted next-generation sequencing platform. An E102_I103del mutation in MAP2K1 was identified in one BRAF wild-type case and confir...

MA BRAF-mutant melanomas tend to develop in preexisting moles. They also tend to affect younger patients; 70% to 80% of the patients who are younger than 30 years when melanoma develops have BRAF-mutant tumors. Conversely, BRAF–wild-type melanomas tend to develop in heavily sun-damaged skin. They tend to affect older patients, especially those aged 70 years and older. Most acral and nearly all ...

BRAF inhibitors have changed the standard therapeutic protocol for advanced or metastatic melanoma which harbored notorious BRAF(V600E) single mutation. However, drug resistance to BRAF inhibitors happens just like other cancer treatment. In this study, we constructed the ideal BRAF(V600E)-modeled structure through homology modeling and introduced the method of structure-based docking or virtua...

BACKGROUND The association between the BRAF mutation and persistence/recurrence was investigated in patients with classical papillary thyroid carcinoma (PTC) at a BRAF mutation prevalent area. METHODS A total of 282 patients with total thyroidectomy and prophylactic central neck dissection were included in this study. The BRAF mutation was evaluated with cytology specimen using dual priming o...