Role of Flavonoids in the Prevention of AhR-Dependent Resistance During Treatment with BRAF Inhibitors.

摘要: BRAF and MEK inhibitors (BRAFi MEKi) are the standard of care for treatment metastatic melanoma in patients with BRAFV600E mutations, greatly improving progression-free survival. However, acquisition resistance to BRAFi MEKi remains a difficult clinical challenge, limited therapeutic options available these patients. Here, we investigated potential natural flavonoids as specific AhR (Aryl hydrocarbon Receptor) transcription factor antagonists combination BRAFi. Experimental design Experiments were performed vitro vivo various human cell lines (mutated BRAFV600E) sensitive or resistant We evaluated role on sensitivity their ability counteract invasive phenotype melanoma. Results Flavonoids highly effective potentiating therapy by increasing delaying pool cells that arise during treatment. As antagonists, counteracted gene expression program associated switching leads an EMT-like phenotype. Conclusions The use opens new opportunities BRAF-resistant disease.