A novel RNAi therapeutic for the treatment of combined B-Raf and MEK inhibitor resistant melanoma

Targeted therapy using small molecules that block cancer promoting proteins is promising for treatment of cancer. However, resistance often develops due to mutations in the cancer cells or expression of different variants of the target, which are "undruggable". For instance, these mechanisms are often involved when melanoma patients develop resistance following combined B-Raf/MEK1 targeted therapy. To overcome drug resistance in melanoma, we will develop a therapy strategy that targets all resistance-driving B-Raf and MEK1 variants. For this purpose, we will employ small gene silencing molecules called siRNAs. This strategy will form the basis of a patient-tailored approach for future cancer therapy.