Counteracting Drug Resistance in Melanoma

Article

A mechanism that leads to resistance to certain targeted therapy drugs for melanoma has been discovered by researchers at the Moffitt Cancer Center in Tampa, Fla.

A mechanism that leads to resistance to certain targeted therapy drugs for melanoma has been discovered by researchers at the Moffitt Cancer Center in Tampa, Fla.

The study was published in the online December issue of Cancer Discovery.

While targeted biological therapy can improve survival for many melanoma patients, they can also develop resistance to these targeted drugs, increasing the risk of regrowth and metastasis.

When it comes to treating melanoma, drugs that target the B-Raf and MEK proteins have been an effective treatment option for these patients. However, many patients over time may become resistant to BRAF and/or MEK inhibitor therapy, which can lead to aggressive disease. The researchers found that melanoma patients who receive treatment with BRAF inhibitor drugs develop more new metastasis compared to those patients on standard chemotherapy. This led researchers to evaluate how this specific drug resistance develops so that better treatment options can be determined.

Using a large screening process, researchers discovered that the resistance and aggressiveness was due to high activity of a cell surface protein known as EphA2-which is apparently also found on glioblastoma stem cells. Interestingly, they also found that discontinuing the BRAF and MEK inhibitor drugs reversed the cells' aggressive behavior.

"This suggests that alternate dose scheduling where BRAF and MEK inhibitors are given to patients intermittently may reduce the aggressiveness of the disease… meaning patients could stay on therapy for more time," said Keiran S. Smalley, PhD, scientific director of the Donald A. Adam Comprehensive Melanoma Research Center of Excellence at Moffitt.  

Targeting EphA2 showed a reduction in aggressive disease behavior in the melanoma cells. This suggests that developing drugs that target EphA2 may inhibit new disease in those patients receiving BRAF and/or MEK therapy.

 

 

 

 

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