Given the significant role of MAPK pathway signaling in impeding JAK2 inhibitor efficacy in MPN, we hypothesized that direct inhibition of ERK1/2 kinases, for which inhibitors have recently become available and have not been specifically explored in MPN, could represent a beneficial therapeutic approach for several reasons: (1) Targeting at the more distal node of ERK1/2 in the MAPK pathway could reduce adaptive signaling changes and reduce the potential for escape from combined JAK2/ERK1/2 inhibition [7]. The gene discussed is MAPK3; the disease is myeloproliferative neoplasm.