Tafinlar (dabrafenib)

BRAFV600E-mutant ATC displays distinct clinical features and improved survival when treated with targeted therapy; ddPCR-based liquid biopsy provides a rapid and sensitive method for BRAFV600E detection and may support timely therapeutic decision-making. Serial LB analysis may contribute to disease monitoring and detection of resistance mechanisms in selected patients.

Using two BRAFV600E mutant melanoma cell lines, Mela14 (treatment-resistant) and Mela16 (treatment-naïve), we investigated whether microtumor arrays could restore cancer stem cell (CSC) characteristics, using ABCB5 and CD271 marker expression, and recapitulate PDTX drug response phenotypes to the BRAF/MEK inhibitor combination dabrafenib/trametinib (DT). These findings suggest that polyacrylamide microtumor arrays can reproduce key features of the in vivo melanoma microenvironment, which may enable rapid, reproducible, and clinically relevant drug sensitivity testing. Therefore, this platform offers potential as a complementary preclinical model for personalized medicine and therapeutic discovery in cancer.

Although paclitaxel and lenvatinib have been used as drug treatments, combination therapy with dabrafenib and trametinib has recently been reported to be effective. Furthermore, lenvatinib, a molecularly targeted agent, shows limited efficacy against ATC and is associated with frequent adverse events. In contrast, combination therapy with dabrafenib and trametinib is considered an effective therapeutic option for patients with BRAF V600E mutation-positive ATC, when appropriate management and monitoring are implemented.

Our findings identify TYRP1 as a marker of a highly proliferative melanoma subpopulation that promotes tumor progression through the GPNMB-Notch1-SOX10/MITF axis. The TYRP1-SOX10-MITF feedback loop represents a key driver of melanoma proliferation and a potential biomarker for stratifying therapeutic response, offering a novel avenue for precision treatment in melanoma.

P=N/A, N=82, Completed, Novartis Pharmaceuticals

The LiBRA study supports liquid biopsy as a prognostic and monitoring tool in BRAF V600E-mutated NSCLC undergoing targeted therapy.

Personalized treatment recommendations were made for 13 patients, and 11 received matched therapies: dabrafenib ± trametinib (n = 9), futibatinib (n = 1), or binimetinib (n = 1). These findings demonstrate frequent actionable alterations in ameloblastoma and clinically meaningful responses of targeted therapies. Incorporating precision oncology into standard care may facilitate personalized, less morbid surgery and improved outcomes in these rare tumors.

Reduced-dose dabrafenib and trametinib were initiated with prophylactic naproxen to mitigate the risk of pyrexia. Treatment has been continued for over 6 months with sustained disease stability. This case suggests that an upfront dose-attenuation strategy combined with proactive toxicity management, including pyrexia prophylaxis, may represent a practical approach to maintain treatment continuity and clinical benefit in selected very elderly or frail patients.

The cytotoxic effects of three MAPK pathway inhibitors (selumetinib, vemurafenib, dabrafenib) were assessed in ATC cell lines and xenograft models via viability assays and 18F-FDG PET/CT. Furthermore, MAPK pathway inhibitors increased radioiodine uptake in ATC cells. The MAPK pathway inhibitors enhance NIS function through two mechanisms: upregulation of NIS expression and increased ARF4-mediated NIS membrane transport.

P3, N=267, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2026 --> Dec 2026

Screening for drugs also revealed AKT1, TP53, and PIK3R4 as druggable hubs, and many drugs (e.g., Everolimus, Dabrafenib, Trabectedin) showing high-affinity interactions. The study discovers new prognostic markers (ATG4A, GABARAPL2, GAPDH) and druggable targets, which could lead to better risk stratification and smarter drug repurposing. While restricted to in silico analyses, the integrative approach provides a basis for subsequent laboratory confirmation and translational development.

P1/2, N=1000, Recruiting, Oslo University Hospital HF | N=6000 --> 1000