gms | German Medical Science

Aim: In melanoma, the most commonly mutated oncogene identified to date is BRAF (40–50%), an upstream mediator of the mitogen-activated protein kinase (MAPK) pathway.

Results: The treatment with selective, targeted drugs is considered feasible for patients with a BRAF, NRAS or cKIT mutation and results in a high rate of confirmed tumor responses. In patients carrying a BRAF mutation and who were treated with BRAF kinase inhibitors or MEK kinase inhibitors the progression free and overall survival is prolonged compared to patients receiving chemotherapy with dacarbazine.

A major problem however, is the development of resistance to these inhibitors through multiple different mechanisms. One approach to overcome resistance is to combine BRAF and MEK inhibitors.

Conclusion: Although, treatments with kinase inhibitors are more efficacious than chemotherapies; however they compete with the newly developed immune checkpoint blockers, and may in future be preferentially applied in second- or xline.