Targeting the JAK-STAT pathway in lymphoma: a focus on pacritinib

Introduction: The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway mediates signaling by cytokine, chemokine and growth factor receptors on cell surface to the nucleus. JAK/STAT pathway is aberrantly activated in a variety of lymphomas, with a dual role of promoting cell survival/proliferation and immune evasion. Areas covered: This review describes the preclinical rationale behind the development of JAK inhibitors in lymphoma, some of which are being evaluated in Phase I/II studies, and summarizes the characteristics and clinical results of different JAK inhibitors in clinical development. Available preclinical and clinical data about JAK inhibition in lymphoid malignancies were reviewed using a PubMed access. To date, pacritinib (SB1518), a selective JAK2/FLT3 inhibitor is the first and only JAK inhibitor that has been evaluated in patients with relapsed lymphoma. Expert opinion: The preclinical rationale behind the development of pacritinib in lymphoproliferative neoplasms is strong, as the deregulation of the JAK/STAT pathway is involved in the pathogenesis of multiple lymphoma subtypes, although with different mechanisms. Pacritinib demonstrated safety and early clinical efficacy in a variety of lymphoma histologic types, providing the first proof of principle of the potential clinical value of targeting JAK/STAT pathway in lymphoma.