Dummer, et al. – Summary

Dummer R, Ramelyte E, Schindler S, Thurigen O, Levesque MP, Koelblinger P. MEK inhibition and immune responses in advanced melanoma. Oncoimmunology. 2017 Aug 10;6(8):e1335843. Available at: https://www.tandfonline.com/doi/full/10.1080/2162402X.2017.1335843


Targeted therapies have shown great efficacy against metastatic melanoma. The first small molecule was efficiently engineered to block the over-active BRAF protein. However, patients rapidly developed resistances. Therefore, a second type of inhibitor was developed in order to block MEK (MEKi) which is a protein downstream of BRAF. In 2012 a phase III study on BRAF-mutated patients showed that 6 months after the start of the treatment, 81% of the patients treated with MEKi were still alive compared to 67% when the patients were treated with chemotherapy. This drug was later on tested on NRAS mutated patients (NEMO study), for whom no other efficient treatment were available. The response rate in MEKi treated patient was 15.5% compared to 6.8% for the chemotherapy treated ones. It was also observed that pre-treatment with immunotherapy improved the outcome of MEKi treatment. In this paper we discuss this finding and the effect of the MEKi treatment on the immune system.


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