P2, N=50, Recruiting, Emory University | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Mar 2028 --> Mar 2029

P4, N=100, Recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2030 --> Dec 2032 | Trial primary completion date: Dec 2029 --> Dec 2032

Four protein kinase inhibitors, R547, GDC-0879, JNJ-7706621 and ABT-869 were found to bind hPIP5K1α via a stable complex formation. The hit molecules display favorable ADME properties and are predicted to be non-carcinogenic. The hit molecules in particular R547, have better binding free energies compared to reference molecule, ISA-2011B.

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.

P2, N=40, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jan 2026