The treatment landscape for myelofibrosis (MF) has reached the molecular era by 
targeting different pathways that are implied in this myeloproliferative 
neoplasm. A few years ago, the first-in-class JAK1/JAK2 inhibitor ruxolitinib, 
demonstrated reductions in both constitutional symptoms and splenomegaly, 
leading to the US FDA approval. The development or worsening of cytopenias in 
patients receiving ruxolitinib uncovered an unmet need that has been addressed 
by alternative approaches. Pacritinib, a dual JAK2 and FLT3 inhibitor which also 
inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated 
splenomegaly and symptom burden, while having limited myelosuppression with 
manageable gastrointestinal toxicity. Herein, we provide an overview of 
pacritinib, from early preclinical studies to the latest and ongoing PAC203 
trial, as an emerging therapy for MF.