Evolving Therapeutic Strategies for the Classic Philadelphia-Negative Myeloproliferative Neoplasms

•Targeting aberrant kinase activity other than that of JAK2 is of significant clinical interest.•Recognition of the genetic basis of MPNs has facilitated the way for drug development.

Despite the emergence of JAK inhibitors, there is a need for disease-modifying treatments for Philadelphia-negative myeloproliferative neoplasms (MPNs). JAK inhibitors ameliorate symptoms and address splenomegaly, but because of the heterogeneous contributors to the disease process, JAK inhibitor monotherapy incompletely addresses the burden of disease. The ever-growing understanding of MPN pathogenesis has provided the rationale for testing novel and targeted therapeutic agents, as monotherapies or in combination, in preclinical and clinical settings. A number of intriguing options have emerged, and it is hoped that further progress will lead to significant changes in the natural history of MPNs.