JAK Inhibitors and other Novel Agents in Myeloproliferative Neoplasms: Are We Hitting the Target?

The discovery of somatic mutations in the JAK-STAT signaling pathway was a major breakthrough in our understanding of the molecular pathogenesis of the myeloproliferative neoplasms (MPNs) polycythemia vera, essential thrombocytosis, and primary myelofibrosis. This finding led to the development of small molecule inhibitors targeting Janus kinase (JAK) 2 and other JAK family members. Currently, there are a number of research and clinical trials ongoing with JAK inhibitors. While the appeal of inhibiting JAK2 is clear, studies to date suggest that JAK2 inhibitor monotherapy might not be sufficient to cause reductions in disease allele burden in MPN patients. There is compelling evidence that JAK inhibitors are improving symptoms and therefore quality of life for patients. It will be important to investigate the efficacy of JAK inhibitors in preclinical and clinical studies to better understand their effects, while at the same time pursuing alternative therapies which might offer benefit to MPN patients alone and in combination with JAK inhibitors.