SNS-314 Mechanism
The process of cell division, or mitosis, plays a critical role in the uncontrolled proliferation that is a hallmark of cancer. During mitosis, a cell aligns duplicate copies of its DNA along a mitotic spindle and subdivides itself through a process called cytokinesis, creating two identical daughter cells. This process is often poorly regulated in cancer, leading to rapid proliferation and tissue growth. Aurora kinases (A, B, and C) play important, though differentiated, roles in mitosis. Aurora A controls the formation of the spindle assembly, while Aurora B ensures that the DNA is appropriately aligned and that cytokinesis proceeds successfully. Less is known about Aurora C, though it is thought to serve many of the same functions as Aurora B. Elevated expression of Aurora A has been detected in a high percentage of colon, breast, ovarian, gastric, and pancreatic tumors. Aurora B and C are also expressed at high levels in primary tumors.
Given the central roles of all three Aurora kinases in regulating mitosis and the association between their overexpression and tumorigenesis, they are being evaluated as potential targets in cancer therapy. SNS-314 is a potent inhibitor of all 3 Aurora kinases. Cells treated with SNS-314 make additional copies of their DNA, but are unable to create functional spindle assemblies or replicate. As a result, these cells are unable to progress, and ultimately die by a variety of mechanisms. Since most normal cells are not undergoing mitosis in their normal settings, SNS-314 is expected to affect only highly proliferating tissues, particularly tumor tissues. SNS-314 is being tested in a Phase 1 trial in patients with advanced solid tumor malignancies.
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| Cells with normal spindle assembly undergoing mitosis | Cells with abnormal spindles due to treatment with SNS-314 | Cells with multiple copies of DNA after failed replication |
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