Zelboraf (vemurafenib)

Through integrated transcriptomic and metabolomic analyses, we demonstrate that BRAFi by vemurafenib (PLX4032) significantly enhances FAO in thyroid cancer cells. The pharmacological inhibition of FAO via thioridazine (Thio) synergizes with BRAFi to suppress tumor growth in vitro, in vivo and in a patient-derived organoid...Consistently, functional studies confirm RUNX1's oncogenic role, as its knockdown reduces cell proliferation, migration, and invasion. In conclusion, our work reveals a metabolic-epigenetic axis underlying adaptive response to BRAFi and identifies RUNX1 as a novel oncogene in thyroid cancer.

Furthermore, short-term treatment of CSPG4-expressing cells with the clinically used mutant active BRAF inhibitor vemurafenib reduced both guidance and speed...The results are discussed in terms of expanding what is known about the potential tumor biology and clinical implications of CSPG4-related impact on malignant invasion during early phases of melanoma progression. The online version contains supplementary material available at 10.1007/s12195-025-00882-x.

We treated the embedded cells or spheroids with different concentrations of either sorafenib or vemurafenib to investigate drug response. We showed that our 3D model was able to reproduce the findings of the in vivo studies, as we observed resistance to the drug in response to sorafenib treatment after 4 weeks. Taken together, the results of this study highlight the potential of user-friendly alginate 3D cell culture models for several aspects of melanoma drug development.

P2, N=10, Completed, HonorHealth Research Institute | Active, not recruiting --> Completed

P1/2, N=50, Recruiting, Universita' Degli Studi Di Perugia | Not yet recruiting --> Recruiting

In particular, these changes were accompanied by the transition towards a stem-like phenotype, characterized by enhanced spherogenic ability and ABCG2 upregulation; interestingly, this led to a reduced in vitro response to the BRAF inhibitor vemurafenib. Mechanistically, an increase in PGC-1α expression was found, resulting in higher mitochondrial mass and activity, ATP synthesis, and ROS overproduction; of note, treatment of melanoma cells with SR-18292 and XCT790, two inactivators of mitochondrial biogenesis, and N-acetylcysteine, a ROS scavenger, successfully counteracted the above EV-related effects, suggesting that mitochondrial function could be targeted to suppress the vesicular interactions between adipose tissue and melanoma. Taken together, these results highlight the crucial role played by EVs in melanoma stroma, pointing out the ability of adipocyte-derived vesicles to sustain cancer aggressiveness via PGC-1α-dependent mitochondrial reprogramming.

Ve combined with Pa exerts a synergistic inhibitory effect on the growth and metastasis of FRO and ARO cells, while promoting apoptosis and cellular redifferentiation. This combination may provide a potential therapeutic strategy for ATC.

The vemurafenib combined with 131I revealed superior efficacy in improving survival and thyroid function recovery in lymph node metastatic BRAF-mutant thyroid cancer.

Compounds 20c and 21c exhibited potent inhibition of EGFR, with IC50 values of 71 and 64 nM, respectively, surpassing the reference erlotinib (IC50 = 80 nM). Moreover, compounds 20c and 21c exhibited BRAFV600E inhibitory action with IC50 values of 49 and 41 nM, respectively, which are somewhat less potent than the reference drug Vemurafenib...Compounds 20c and 21c showed a notable decrease in TNF-α and IL-6 levels compared with dexamethasone, suggesting an immunomodulatory effect. Molecular docking further validated the favorable orientation of 20c and 21c within the ATP-binding pocket of EGFR and BRAFV600E. These findings underscore compounds 20c and 21c as innovative dual-target scaffolds with significant promise for anticancer drug development.

Furthermore, we show that secondary resistance induced by prolonged exposure of melanoma cells to BRAF inhibitor is associated with reduced FGD1 levels. These findings highlight the importance of FGD1 in melanoma progression and the acquisition of secondary resistance, positioning the FGD1-mediated signaling pathway as a putative therapeutic target.

Melanoma A375 (vemurafenib [VEM]-sensitive) and A375R (VEM-resistant) cells were exposed to eIF4Fi RocA at varying doses and durations in vitro...Combined CR-1-31-B, EZH2i, and AKT1i effectively overcame resistance to RocA and VEM resistance both in vitro and in vivo. The eIF4F complex inhibitor reactivates ERK1/2-EZH2 and AKT1 signaling pathways, resulting in resistance to both eIF4Fi and VEM. Combined administration of an eIF4Fi with EZH2 and AKT1 inhibitors effectively enhances sensitivity to both eIF4F complex and BRAF inhibitors.

She was initially treated with Vemurafenib and Cobimetinib, achieving complete remission. However, due to cumulative toxicities, therapy was switched to Encorafenib and Binimetinib in February 2023...Management included Binimetinib dose reduction and topical ketorolac, resulting in initial improvement, although the CME recurred several months later...The patient ultimately began immunotherapy with Nivolumab and Ipilimumab, but died in February 2024 due to refractory abdominal septic shock. This case highlights the importance of early ophthalmologic monitoring and interdisciplinary collaboration in patients receiving MEK inhibitors.