Introduction: Kinesin spindle protein (KSP) is indispensable for the proper separation of spindle poles during mitosis. Importantly, this protein is expressed only in cells undergoing cell division and hence represents an appealing target for the treatment of cancer. Many KSP inhibitors have demonstrated a strong antitumoral effect in vitro, however, they have exhibited only limited activity in clinical trials. By contrast, the KSP inhibitor filanesib has demonstrated clinical efficacy in patients with multiple myeloma (MM).Areas covered: This article provides a comprehensive overview about the progress to date in the preclinical and clinical development of filanesib for the treatment of cancer, and particularly, MM.Expert opinion: Responses observed with filanesib alone or in combination with dexamethasone were encouraging in MM. However, the subsequent appearance of highly effective novel agents such as monoclonal antibodies, has hindered the development of agents such as filanesib that exhibit a more limited activity. Nevertheless, filanesib has shown interesting results for some patients when combined with carfilzomib and pomalidomide. Most importantly, the availability of a biomarker of response such as alpha 1-acid glycoprotein (AAG), could be key to the identification of patients that could benefit most from these combinations.
Keywords: ARRY-520; Eg5; KSP; filanesib; multiple myeloma.