Activation of the ErbB3-AKT axis promotes melanoma cell survival and proliferation in response to RAF/MEK inhibition

Background Therapy of advanced melanoma has been improved with the advent of BRAF inhibitors. However, a limitation to such treatment is the occurrence of resistance. Several mechanisms have been implied in the development of resistance, which in most cases lead to downstream MEK reactivation. In order to overcome resistance MEK inhibitors are being clinically developed with promising results. However, also in this case resistance inevitably occurs. It is commonly believed that the establishment of resistance is facilitated by adaptive changes that take place in cancer cells shortly after exposure to kinase inhibitors. Our laboratory is interested in the identification of these early adaptive changes with the intent to discover additional targets for therapeutic intervention. Methods