Search

However, there is still a considerable need for effective targeted therapies for other melanoma subgroups with constitutive MAPK activation, such as RAS- and NF-1-mutated tumors, as well as for therapeutic options targeting MAPK pathway inhibitor resistant BRAF-mutated melanomas, which commonly exhibit a striking reactivation of this pathway. Based on that, our work "Inhibition of RSK family members can effectively target malignant melanoma cells with MAPK pathway hyperactivation" assessed a potential functional role of the p90 ribosomal S6 kinases and their inhibition in different MAPK pathway-driven genetic melanoma subgroups. In line with a pronounced reactivation of the MAPK pathway in the case of MAPK pathway inhibitor resistance, we observed a further increase in RSK activity in BRAF-mutated melanoma cells with acquired MAPK pathway inhibitor resistance both in an in vitro model system and in tumor biopsies from stage IV melanoma patients which progressed under MAPK pathway inhibitor therapy. We found that IL-9-producing TH cells are better described as a subpopulation of TH2 cells that express IL-9 transiently post activation, rather than as a bona fide TH cell lineage. [Extracted from the article]