The authors demonstrate that the mutation results in increased BRAF homodimerization, which in turn is targetable with second-generation BRAF inhibitors.<i>Cancer Discov; 8(9); 1064-5.
The results revealed that compounds 8c and 8d showed almost same BRAF inhibitory activity and were discovered to be potent inhibitors of cancer cell proliferation and were also observed to be strong Tubulin inhibitors.
In nearly all MYD88-wild-type DLBCL-LT, we found cancer-promoting mutations that either activate the NF-κB pathway through alternative genes (NFKBIE or REL) or activate other canonical cancer pathways (BRAF, MED12, PIK3R1, and STAT3).
With advances in RAF inhibitors and second-generation inhibitors including encorafenib and vemurafenib, which have been approved for treating BRAF-V600Emalignancies, the combinatorial therapeutic strategies of RAF inhibitors elicit remarkable responses in patients with BRAF-V600E mCRC.
In human cancer, Raf activity is frequently dysregulated due to mutations in the Raf family member B-Raf or to alterations in upstream Raf regulators, including Ras and receptor tyrosine kinases.
Our findings provide evidence of critical survival signals in BRAF non-V600E mutant cancers, which could pave the way for effective treatment of these cancers.
The presence of the noninheritable V600EBRAF mutation in this family supports Knudson's "double-hit" hypothesis for cancer development and suggests the involvement of more than 1 gene in the clinical expression of FNMTC.
Here, we aimed to model the mechanism of resistance to ERK inhibitors.<b>Experimental Design:</b> We tested five structurally different ATP-competitive ERK inhibitors representing three different scaffolds on BRAF/RAS-mutant cancer cell lines of different tissue types to generate resistant lines.
Clinicopathological features such as age, gender, tumour location, tumour size, TgAb and TPOAb levels, capsular invasion, multifocality, central lymph node metastases and BRAF mutation were examined to evaluate the rate of malignancy in the contralateral thyroid nodules.
RHEB Y35N expressing cells undergo cancer transformation due to decreased interaction between RHEB and BRAF resulting in overactive RAF/MEK/ERK signaling.
Thyroid carcinomas (TCs) bearing BRAF mutations represent approximately 26-53% of human thyroid malignancies and, differently from melanomas, are poorly sensitive to BRAF inhibitors (BRAFi), and develop acquired resistance through activation of alternative signaling pathways.
For the 37 cases cytologists favored to be cPTC, 31 (84%) had a molecular result that supported malignancy (28 BRAFV600E mutations, 2 NTRK1 fusions, 1 AGK-BRAF fusion).
The expression profile of integrin receptors and osteopontin in thyroid malignancies varies depending on the tumor progression rate and presence of BRAFV600E mutation.
The Idylla NRAS-BRAF mutation test has been developed for the qualitative detection of mutations in <i>NRAS</i> and <i>BRAF</i> oncogenes, facilitating genetic profiling of patients with cancer.
Through structural analysis and mechanistic studies with BRAF and mitogen-activated protein kinase (MEK) inhibitors, we describe how kinase-dependent and -independent functions of MAPK signaling components regulate KRAS-driven tumorigenesis and how these insights can be used to treat RAS mutant cancers with small molecule kinase inhibitors.