Despite the promise of new targeted treatments such as BRAF and MEK inhibitors, advanced melanoma patients often have different responses due to genetic variability. Now researchers say they have identified a way to better predict these responses. In their study published in EBioMedicine, researchers from Moffitt Cancer Center’s Donald A. Adam Melanoma and Skin Cancer Center of Excellence found that certain differences can predict responses to initial BRAF inhibitor therapy, and that leveraging these differences may improve patient outcomes.
The researchers set out to determine how differences between cells of a single tumour lead to better responses to BRAF/MEK inhibitors in certain patients. They assessed the variability of melanoma cells and their responses to BRAF inhibitor treatment by analysing the RNA expression patterns in single cells from melanoma cell lines and patient samples, and they discovered that melanoma cells can reside within four different states with distinct patterns of gene expression.
The researchers also found that maintaining a population of cells within the drug-sensitive State 1 was critical to maintaining drug sensitivity, and they created a mathematical model to show that it is possible to maintain drug-sensitive cell populations in State 1 by using an adaptive dosing schedule.
The researchers then validated their mathematical model in mouse experiments, and they say that their studies in cell lines and mouse models could lead to improved treatment approaches for patients.
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Source: Medical Xpress