Therapeutics: Aurora kinase A (AURKA; Aurora-A)

Mouse studies suggest AURKA inhibitors could help treat primary myelofibrosis (PMF). Levels of AURKA were higher on hematopoietic progenitor cells in blood from PMF patients than from healthy controls, and in the patient progenitor cells, the AURKA inhibitor alisertib decreased growth compared with vehicle. In a mouse model of PMF, AURKA knockout or alisertib decreased white blood cell and platelet production, spleen and liver weight, and tumor burden and fibrosis compared with normal AURKA expression or vehicle. Also in the PMF model, alisertib plus subtherapeutic doses of Jakavi ruxolitinib decreased disease-related megakaryocyte burden and tumor burden compared with either agent alone. Next steps include Phase I testing of alisertib to treat PMF and acute megakaryoblastic leukemia (AMKL).

Takeda Pharmaceutical Co. Ltd. has alisertib (MLN8237) in Phase I to Phase II testing to treat multiple solid tumor types and lymphomas...