Approved BRAF inhibitors have shown limited clinical benefit due to recurrent disease progression. In a recent Cancer Discovery paper, Yaeger et al. show that a next-generation BRAF inhibitor, PF-07799933, has widespread therapeutic activity in experimental models and patients who were refractory to treatment with approved BRAF inhibitors.
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http://dx.doi.org/10.1016/j.trecan.2024.05.009 | DOI Listing |
J Clin Med
December 2024
Department of Dental Medicine, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
: Although BRAF inhibitors, such as vemurafenib, produce a marked response in patients with advanced melanoma with a BRAF V600 mutation, they eventually develop resistance to this treatment. To address this issue, vemurafenib is increasingly combined with the MEK inhibitor cobimetinib, leading to improved response rates and enhanced survival. However, this treatment modality is associated with numerous side effects.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Medical Oncology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan.
Immune checkpoint inhibitors (ICIs) are effective in treating recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but only 20% of patients achieve durable responses. This study evaluated circulating tumor DNA (ctDNA) as a real-time biomarker for monitoring treatment response in HNSCC. The SHIZUKU-HN study prospectively collected and analyzed serial plasma samples (n = 27) from HNSCC patients undergoing ICIs, using Guardant360 to assess ctDNA variant allele frequency (VAF) and genetic mutations.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Department of Pediatrics, West China Second University Hospital, Sichuan University, Sichuan, China.
Langerhans cell histiocytosis (LCH) is characterized genetically by diverse gene mutations of the mitogen-activated protein kinase signaling cascade. BRAFN486_T491delinsK mutation is a rare mutation that involves the β2-αC ring domain, causing activation of the mitogen-activated protein kinase pathway, and is predicted to be resistant to the chemotherapy and BRAFV600E inhibitor in adult LCH cases. Here, we report a childhood LCH case with this novel BRAF mutation and had a good response to conventional chemotherapy.
View Article and Find Full Text PDFRare Tumors
January 2025
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA.
Ameloblastoma is a rare tumor arising from odontogenic cells that is benign, yet locally aggressive. Metastasizing ameloblastoma (METAM) is an ultra-rare ameloblastoma variant in which both primary and secondary tumors have histological features of benign ameloblastoma. This is a case report of a patient who presented with a jaw mass and subsequent lung metastases, later diagnosed as METAM.
View Article and Find Full Text PDFClin Exp Pharmacol Physiol
March 2025
Department of Dermatology, Fudan University Huashan Hospital, Shanghai, China.
BRAF inhibitors (BRAFi) represent a cornerstone in melanoma therapy due to their high efficacy. However, the emergence of resistance causes a significant challenge to their clinical utility. This study aims to investigate the potential of diclofenac as a sensitizer for BRAFi therapy in melanoma and to elucidate its underlying mechanism.
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