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**Selinexor + ruxolitinib** is an investigational, oral, small molecule combination therapy for the treatment of myelofibrosis (MF), particularly in JAK inhibitor-naïve patients. Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) compound that targets Exportin 1 (XPO1), leading to increased nuclear retention of tumor suppressor proteins such as p53 and inhibition of NF-κB signaling, promoting cell cycle arrest and apoptosis in malignant cells. Ruxolitinib is an oral JAK1/2 inhibitor that suppresses the JAK-STAT pathway, decreasing inflammation and aberrant cell proliferation in myeloproliferative disorders. The combination is currently being studied for its synergistic effects, providing efficacy via orthogonal mechanisms—JAK-STAT pathway inhibition (by ruxolitinib) and nuclear export inhibition (by selinexor), as well as downstream suppression of pro-inflammatory cytokines. Primary clinical development is aimed at improving symptom burden and spleen volume in myelofibrosis[1][2][3][4][5][7].
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