Zelboraf (vemurafenib)

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.

Our results highlight that both hypoxia and therapeutic pressure modulate tumor progression in a complex, context-dependent manner.

Notably, δ-TT restored responsiveness to vemurafenib, indicating a synergistic interaction in resistant melanoma cells. Overall, these findings provide mechanistic evidence supporting a potential role for δ-TT as a modulator of drug response and support further investigation of δ-TT-based combination strategies to overcome therapeutic resistance in melanoma.

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

Vemurafenib markedly inhibited HCC cell proliferation and metastasis, which was accompanied by a pronounced induction of apoptosis and G0/G1 phase cell-cycle arrest. At the signaling level, these cellular responses were linked to enhanced JNK activation and the suppression of AKT phosphorylation, suggesting that vemurafenib may serve as a potential therapeutic agent for HCC.

CST also reduced the viability and migration of Vemurafenib-resistant A375 cells, accompanied by the downregulation of multiple resistance-associated genes...Mechanistically, CST downregulates key pro-tumorigenic and pro-fibrotic signaling molecules, including LOXL2, PDGFRB, CCN2, and DDIT4, which are associated with extracellular-matrix remodeling, growth factor signaling, and cellular stress adaptation. These findings identify CST as a novel regulator of tumor survival and metastatic potential, supporting its therapeutic potential as a peptide-based anti-cancer agent.

P1/2, N=12, Active, not recruiting, Instytut Matki I Dziecka | Recruiting --> Active, not recruiting

RR is a reproducible and clinically relevant phenomenon following MAPKi discontinuation in pLGG. Standardized definitions, structured post-discontinuation surveillance, and prospective evaluation of treatment duration and dose-tapering strategies are needed to optimize MAPKi discontinuation and long-term disease management in patients with pLGG.

The detachable MN consisted of an innermost poly (ethylene glycol) diacrylate extraction layer, an outer gelatin methacryloyl drug-loaded layer containing Vemurafenib and black phosphorus (BP), and a polyvinyl alcohol connection layer designed for thermal detachment...It enabled dPCR-based monitoring of MCAM and BRAF genes, including the drug-resistant V600E polymorphism, with detection limits of 223 copies/µL, along with digital proximity ligation assay detection of the protein markers IL-6, VEGF, and Ki-67 at 0.64 pg/mL. This well-designed biosystem highlighted its capability to interact with the pathophysiological environment, providing a preclinical proof-of-concept for minimally invasive theranostics in superficial tumors.

P2, N=50, Completed, University College, London | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Nov 2025 | Trial primary completion date: May 2026 --> Nov 2025

P2, N=64, Completed, Mayo Clinic | Active, not recruiting --> Completed

Comprehensive molecular testing in SGC may allow access to MMT, with a subset of patients experiencing clinical benefit from this strategy.