Zelboraf (vemurafenib)

Additionally, consistent "Rho GTPase signaling" changes were observed across both proteomic and phosphoproteomic analyses, underscoring the functional reactivation of this pathway in resistant tumors. In summary, these findings reveal molecular signatures of early response and acquired resistance to vemurafenib and offer a valuable resource for future investigation of BRAF-targeted therapy.

These findings suggest that delivering vemurafenib in polymeric nanocapsules produces delayed but sustained cytotoxic and apoptotic effects in ATC cells in vitro, warranting further investigation of this nanocarrier approach for thyroid cancer treatment. Altogether, the biological results reported in this study are derived from in vitro experiments and require further validation in in vivo models.

Furthermore, the combination of vemurafenib with cysmethynil, a proof-of-concept ICMT inhibitor, showed efficacy in combating RAC1P29S-driven resistance of BRAFV600E melanoma cells in both in vitro and in vivo settings...We further validated the role of TAZ in RAC1P29S-driven resistance by demonstrating that introducing a constitutively-active TAZ mutant enhanced the resistance to MAPK pathway inhibitors in native cells, phenocopying the effect of RAC1P29S. The novel application of MAPK pathway inhibitors and cysmethynil combination in RAC1P29S-driven MAPK-pathway-inhibitor-resistant melanoma cells extends the potential utility of ICMT inhibitors, and also provides a new mechanism for targeting ICMT in cancer.

P2, N=64, Completed, University of Sydney | Active, not recruiting --> Completed

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.