P4, N=165, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

P1, N=16, Recruiting, Pfizer

P2, N=254, Recruiting, Fore Biotherapeutics | N=134 --> 254

Avutometinib plus defactinib represents a promising targeted therapeutic strategy for recurrent LGSOC, particularly in patients with KRAS-mutant tumors. If confirmed in phase III trials, this combination may establish a molecularly informed disease-specific treatment paradigm with the potential for more durable disease control than existing therapies.

Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the FDA for clinical use. Molecular dynamics and metadynamics simulations were performed in the Desmond module of the academic version of the Schrödinger-Maestro 2021-4 program, utilizing the OPLS-2005 force field. Finally, all the protein figures presented in this article were made in the PyMOL program and the RMSD graphics were made in the statistical package R and RStudio 2025.05.1.

Redifferentiation approaches using MAPK pathway inhibitors such as selumetinib and dabrafenib can restore iodine uptake in selected patients, although the overall clinical applicability of these strategies remains under evaluation. A better understanding of these mechanisms may support improved biologic stratification and more selective therapeutic decision-making in radioiodine-refractory DTC.

TAZ loss represses the UPR, reverses the inhibition of protein synthesis, and triggers increased cell death by ferroptosis in dabrafenib-treated ATC. Collectively, our findings unveil TAZ as a new target to overcome resistance to BRAF inhibitors in undifferentiated thyroid cancer.

P1/2, N=105, Not yet recruiting, Institut De Recherches Internationales Servier IRIS

P2, N=15, Completed, Scripps Health | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2026 --> Apr 2026

Building on these findings, we investigated the therapeutic benefit of combining the EGFR inhibitor erlotinib with the novel pan-RAF inhibitor LXH-254. hese results contrast with previous reports of efficacy from monotherapies in xenograft models, highlighting the limitations of current preclinical approaches. Our findings underscore the need to develop more effective pathway-targeted inhibitors, and preclinical models that predict clinical outcomes more accurately.

Vemurafenib increases miR-31-5p in keratinocyte-derived exosomes, which suppresses ALKBH1 and elevates RNA m6A in melanoma cells, thereby promoting proliferation and reducing vemurafenib sensitivity. Targeting the miR-31-5p/ALKBH1 axis and m6A modification may offer a potential therapeutic strategy to enhance vemurafenib sensitivity in BRAFV600E melanoma cells.

P1, N=267, Recruiting, Pfizer | Trial completion date: May 2030 --> Aug 2030 | Trial primary completion date: Nov 2028 --> Feb 2029