Melanoma is a deadly tumor which in recent years has been successfully treated with immune checkpoint inhibitors as PD-1/PD-L1 and CTLA-4 inhibitors and targeted therapy as BRAF and MEK inhibitors.
Using laser-capture microdissection and droplet digital PCR, we investigated whether endosalpingiosis harbours the driver mutations in BRAF and KRAS that characterise ovarian low-grade serous neoplasms.
We then knocked a mutation into BRAF encoding the V600E substitution and overexpressed the GREM1 transgene; the organoids were transplanted into colons of NOG mice and growth of xenograft tumors was measured.
For example, we found that TP53 mutations decrease sensitivity to BRAF inhibitors in BRAF mutated cell lines and patient tumors, suggesting a therapeutic benefit of combining inhibition of oncogenic BRAF with reactivation of the tumor suppressor TP53.
No significant differences regarding additional imaging features emerged between BRAFV600E-mutant and wild-type lesions, with the exception of the number of tumors with cystic components, significantly higher in BRAFV600E-mutant PAs (p = 0.011) CONCLUSION: Assessment of the DWI characteristics of GGs and PAs may assist in predicting BRAFV600E status, suggesting a radiogenomic correlation and prompt molecular characterization of these tumors.
BRAF inhibitors alone or in combination with MEK inhibitors fail to eradicate the tumor in most patients due to combinations of intrinsic or acquired resistance.
In metastatic melanoma the BRAF oncogenic pathway is a master regulator of this process, highlighting the importance of metabolic reprogramming in the pathogenesis of this tumor and offering potential therapeutic approaches.
Thirty-six tumor tissues from BRAF wild-type melanoma patients at Seoul National University Hospital (SNUH) were collected and deep-sequenced using the SNUH FIRST-Cancer NGS panel to assess single nucleotide variants, small insertions/deletions, copy number variations, and structural variations to estimate tumor mutation burden (TMB).
Here, we quantitated <i>in vivo</i> ERK1/2 activity and tumor response associated with resistance to combined BRAF and MEK inhibition in mutant BRAF xenografts.
Techniques for the accurate identification of activating mutations of BRAF in metastatic melanoma are of great clinical importance, due to the availability of targeted therapies for these tumors.
We hypothesized that proteomic data would complement mutation status to identify vemurafenib-sensitive tumors and effective co-treatments for BRAF-V600Etumors with inherent resistance.
The goal of this work is to determine if imaging features of the primary tumor and the pattern of metastasis correlate with the functional class of BRAF mutation.
We found a high frequency (90.0%) of BRAFV600E mutations, and mutation status was not associated with clinicopathological factors including age, tumor location, and recurrence.
Molecular analysis of a previously surgically removed tumor showed a BRAFV600E mutation and thus, combined targeted inhibition of the MAPK/ERK signaling pathway using a BRAF inhibitor and a MEK inhibitor was started.
In the case of BRAF-V600E mutant melanoma, ERK inhibition has emerged as a viable clinical approach to abrogate signaling through the ERK pathway, even in cases where MEK and Raf inhibitor treatments fail to induce tumor regression due to resistance mechanisms.
The 4-year progression-free survival rate, but not overall survival rate, was significantly higher in patients with KRAS-negative tumors than in those with KRAS-positive tumors (<i>P</i> < 0.05), whereas BRAF, MEK, and ERK expression was unrelated to survival.
Associations between BRAFV600E and TERT promoter mutations and clinicopathological features, Tumor-Node-Metastasis stage, initial risk, response to therapy, follow-up, and final disease outcome were assessed according to American Thyroid Association 2015 criteria and the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system.Median follow-up was 120 months.
BRAF and MEK inhibitors (BRAFi and MEKi) are actively used for the treatment of metastatic melanoma in patients with BRAF<sup>V600E</sup> mutation in their tumors.
Specifically, we show that entinostat dramatically enhances tumor regression when combined with BRAF/MEK inhibitors, in both models that are sensitive or relatively resistant to these agents.
The presence of BRAF-V600E mutations in ameloblastoma was related to decreased levels of glycerol in comparison with tumors carrying only wild-type alleles of this gene.