The BRAF inhibitor vemurafenib has become an important treatment option for melanoma patients, the majority of whom have a BRAF(V600E) mutation driving their malignancy. However, this same agent does not generally benefit colon cancer patients who have the BRAF(V600E) mutation. Recent work suggests that BRAF(V600E) inhibition by vemurafenib results in decreased negative feedback to the epidermal growth factor receptor (EGFR) pathway and that the different clinical responses are due to differences in the amount of EGFR present in these two cancers. The experimental work that identified the feedback signaling was an elegant mix of functional genomic approaches and focused, hypothesis-driven cellular and molecular biology. The results of these studies suggest that combined treatment of BRAF(V600E)-driven colon cancers with both vemurafenib and EGFR inhibitors is worth clinical evaluation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/scisignal.2003354 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Management of asynchronous multifocal adult glioblastoma with loss of BRAF -mutant clonality: a case report.
Acta Neuropathol Commun
January 2025
Department of Neuro-Oncology, Columbia University Irving Medical Center, 710 W. 168th Street, New York, NY, 10032, USA.
Glioblastoma (GBM) classification involves a combination of histological and molecular signatures including IDH1/2 mutation, TERT promoter mutation, and EGFR amplification. Non-canonical mutations such as BRAF, found in 1-2% of GBMs, activate the MEK-ERK signaling pathway. This mutation can be targeted by small molecule inhibitors, offering therapeutic potential for GBM.
View Article and Find Full Text PDFDetection of Circulating Tumor DNA in Liquid Biopsy: Current Techniques and Potential Applications in Melanoma.
Int J Mol Sci
January 2025
August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rosselló 149, 08036 Barcelona, Spain.
The treatment landscape for advanced melanoma has transformed significantly with the advent of BRAF and MEK inhibitors (BRAF/MEKi) targeting V600 mutations, as well as immune checkpoint inhibitors (ICI) like anti-PD-1 monotherapy or its combinations with anti-CTLA-4 or anti-LAG-3. Despite that, many patients still do not benefit from these treatments at all or develop resistance mechanisms. Therefore, prognostic and predictive biomarkers are needed to identify patients who should switch or escalate their treatment strategies or initiate an intensive follow-up.
View Article and Find Full Text PDFPTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.
J Exp Med
March 2025
Institute of Cancer Research, Shenzhen Bay Laboratory , Shenzhen, China.
BRAF mutations drive initiation and progression of various tumors. While BRAF inhibitors are effective in BRAF-mutant melanoma patients, intrinsic or acquired resistance to these therapies is common. Here, we identify non-receptor-type protein tyrosine phosphatase 23 (PTPN23) as an alternative effective target in BRAF-mutant cancer cells.
View Article and Find Full Text PDFBRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center's experience.
Front Oncol
January 2025
Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, GA, United States.
Background: Pediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAF alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAF altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAF altered pLGG.
View Article and Find Full Text PDFBRAF regulates circPSD3/miR-526b/RAP2A axis to hinder papillary thyroid carcinoma progression.
BMC Mol Cell Biol
January 2025
Department of Ultrasound, Henan Provincial People's Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan, 450000, China.
Background: Papillary thyroid carcinoma (PTC) is a common malignant tumor. BRAF mutation has become a common molecular event in PTC pathogenesis. Circular RNA PSD3 (circPSD3) is known to be highly expressed in PTC.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!