We report here a patient on encorafenib who developed numerous new pigmented lesions within 3 weeks of therapy...This case underscores that BRAF inhibition may enhance PRAME expression in benign melanocytic nevi, potentially through mechanisms involving mitogen-activated protein kinase (MAPK) activation, altered Erk phosphorylation, or disruption of retinoic acid (RA) signaling. This case also brings awareness to the potential of medication-induced PRAME expression and encourages both dermatologists and dermatopathologists to avoid overdiagnosis as PRAME continues to gain prominence as a diagnostic biomarker.

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.

In a compound screen on melanoma cells, we identified FX-11 as one of the compounds inhibiting the growth of sensitive and Encorafenib/Binimetinib-resistant 624Mel and Wm3248 melanoma cells. Taken together, we provide evidence that FX-11 inhibits the growth of melanoma cells, including drug-resistant ones, through an AMPK-dependent mechanism by acting as a mitochondrial uncoupler. Our data do not support that FX-11 acts as an LDH inhibitor.

Combination therapy of encorafenib plus binimetinib for unresectable BRAF V600-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.