Aurora Kinase inhibitors
Summary
Cell cycle inhibitors represent a key approach to the treatment of cancer. Therapeutic agents have traditionally targeted early stages of the cell cycle (ie the G1/S phase checkpoint or the S phase) or mitotic spindle formation as exemplified by the alkaloids. Recently a new approach to cell cycle regulation has emerged with the identification of the Aurora kinase family. This report evaluates this exciting area of drug discoveryAurora Kinase inhibitors
The dawn of a new approach to cancer
Cell cycle inhibitors represent a key approach to the treatment of cancer. Therapeutic agents have traditionally targeted early stages of the cell cycle (ie the G1/S phase checkpoint or the S phase) or mitotic spindle formation as exemplified by the alkaloids. Recently a new approach to cell cycle regulation has emerged with the identification of the Aurora kinase family. This family plays a role in later stages of the cell cycle from the G2/M check point all the way through to the mitotic checkpoint and late mitosis.
Aurora Kinase Inhibitors: The dawn of a new approach to cancer was written as a target evaluation/drug development update report. This analysis was intended to provide a framework for all organizations considering entry into this exciting field or those already in the field but who require competitive intelligence within the area. The report:
- Introduces the Aurora kinases
- Analyzes the proof of concept supporting the development of aurora kinase inhibitors for the treatment of cancer
- Discusses mechanism of action
- Evaluates drugs in development
- Provides strategic guidance on kinase selectivity
- Discusses the promise and risks of kinase inhibitors
- Offers competitive intelligence discussing how Aurora kinase inhibitors would fit into the current oncology treatment area. The report compares this class with existing and emerging classes and evaluates the part that Aurora kinase inhibitors could play in the combinatorial approach to cancer
Our understanding of the Aurora kinase family and its role in cell division has advanced over recent years and the drug discovery community is now in a good position to judge the proof of concept supporting the development of kinase inhibitors. The body of data reported in Aurora Kinase Inhibitors: The dawn of a new approach to cancer suggests the kinase family meets many of the criteria that need to be satisfied to put drug discovery efforts into the development of kinase inhibitors. There is bountiful evidence to support a role for of Aurora kinases in cellular events that become defective in cancer, namely cell cycling; overexpression of the kinases in various cancers is convincing; manipulations that increase Aurora kinase activity have been shown to promote various cellular events consistent with tumorigenesis and; perhaps most convincingly the farthest advanced inhibitor to date has just entered the clinic having demonstrated impressive anticancer efficacy in well designed and pertinent preclinical models. A number of issues are however outstanding that should be addressed in order to optimize the development of the kinase field. These include an appreciation of how targeted to cancer cells Aurora kinase inhibitors can be; likely interactions (positive or negative) with existing agents; at which stage in tumor progression such inhibitors may be most effective; and an understanding of the benefits and risks of producing catastrophic mitotic damage such is seen with Aurora kinase inhibition. This report offers a strategic analysis of each of these issues, evaluates the first wave of kinase inhibitors, and makes recommendations on future directions.
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