Aurora Kinase Inhibitor
Virtually all cells in the body divide and reproduce by a complex process known as mitosis. At first, DNA-containing chromosomes duplicate themselves into two identical copies. Then part of the cell structure known as microtubules form a spindle-like array displayed in a fiber-like configuration. These microtubules attach to the duplicated chromosomes and function to pull the chromosomes apart toward opposing poles of the cell. The spindle breaks down, and the cell membrane pinches off along the equator of the mother cell creating two identical daughter cells. (See illustration).
This very complicated process of cell division requires the assistance of many proteins to serve as regulators. One of the most important is called aurora-A kinase, which regulates the stability of the spindle microtubules, and the attachment and alignment of the chromosomes. The essential function of aurora-A kinase is to assure that the daughter cells are exact copies of the mother cell.
Researchers have made the interesting discovery that many types of cancer cells contain too much aurora-A kinase (called “overexpression” or “amplification”). For example, one study showed that 94% of invading breast cancer cells had too much aurora-A kinase, while the surrounding normal tissue had normal levels. High levels within cells impair their ability to divide properly and separate into daughter cells. This impairment of proper cell division results in undivided abnormal single cells with too many chromosomes. Since increased numbers of chromosomes are traits of many cancer cells, it seemed logical to develop a drug that targets the high levels of tumor aurora-A kinase in an attempt to stop cancer cell development and restore orderly cell division.
A novel aurora-A kinase inhibitor, MLN8237, is being studied at Tower Cancer Research Foundation in an important clinical trial. Preliminary animal and human research studies at other institutions have confirmed that this highly selective inhibitor has anti-tumor effects in certain cancers and blood malignancies. Our trial investigates further the effectiveness of this agent in a variety of cancers, especially lung, breast, head and neck, and gastrointestinal.
There is now a large body of data implying that aurora-A kinase amplification is an important cause of cancer. Hopefully, our studies may prove that blocking it with this inhibitor will provide an important treatment breakthrough.