Melanoma variability at the single-cell level predicts treatment responses

Source: Medical Express, October 2019

Patients with advanced melanoma have been able to live longer because of several newly approved targeted treatment options, including BRAF and MEK inhibitors. However, patients will often have different responses to the same treatment due to genetic variability. Melanoma varies from patient to patient, but genetic variability is also prevalent among different cells from a single tumor. In a new study published in EBioMedicine, researchers with Moffitt Cancer Center’s Donald A. Adam Melanoma and Skin Cancer Center of Excellence reveal that differences at the single-cell level can predict responses to initial BRAF inhibitor therapy, and that leveraging these differences may improve patient outcomes.

Approximately half of all melanoma patients have mutations in the BRAF gene that promote cancer growth. Drugs that target BRAF and the downstream signaling protein MEK have significantly improved patient outcomes, but patients with advanced melanoma are rarely cured with these drugs and most will eventually develop  and relapse. However, some patients with BRAF-mutated melanoma can be successfully retreated with BRAF or MEK inhibitors. Moffitt researchers wanted to determine how differences between  of a single tumor lead to better responses to BRAF/MEK inhibitors in certain patients.

The research team assessed the variability of melanoma cells and their responses to BRAF inhibitor treatment by analyzing the RNA expression patterns in  from melanoma cell lines and patient samples. They discovered that melanoma cells can reside within four different states with distinct patterns of gene expression. Their analysis predicted the following:

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