Clapper, Patti, Schweizer and Mason

A recent article published in the April edition of Oncology Times demonstrated that Aurora kinase may be used as a therapeutic modality in treating mesothelioma. Mesothelioma is a rare but aggressive cancer caused by exposure to asbestos. Mesothelioma is a malignancy that affects the pleura (lungs), peritoneum (abdomen), and pericardium (heart). 

 

The majority of patients were exposed to asbestos decades prior to any symptom development, making the disease very challenging to diagnose and treat. The prognosis for mesothelioma remains quite poor, with median survival times ranging from 8 – 14 months. To date, there is no known cure and treatments often have little effect. Therefore, the aim of mesothelioma treatment is to relieve symptoms and improve quality of life.

 

One idea being researched is to find inhibitors that destroy or decrease cell growth in mesothelioma, thereby slowing the progression of the disease and its accompanying symptoms. Aurora kinases are being researched as drug targets in cancer therapies, including those used for mesothelioma.

 

There are three types of human aurora kinases, A, B, and C. Aurora A and B are often overexpressed in mesothelioma, and therefore research has been focusing on these two as they appear to play a role in oncogenesis. Oncogenesis is causation of tumor development. Aurora C has not been shown to play a role, however A and B have and are often connected in expression.

 

Malignant tumor cells are defined by inappropriate growth accompanied by invasion into nearby tissues and metastases to other distant sites within the body. Certain chemotherapeutic agents have been shown to selectively kill tumor cells, slowing or stopping proliferation of the malignancy. The goal is to find pharmaceuticals that will target such proteins with minimum collateral damage to healthy cells and tissue. Proteins such as aurora kinases that are associated with cell growth and cycles have shown potential to be used as anticancer drug targets.

 

The idea is that these proteins are overexpressed in mesothelioma and can be used as targets for administration of anticancer drugs while at the same time protecting surrounding normal cells. Drugs that would select and inhibit aurora kinases A and B are being studies in clinical trials. The following drugs have shown preliminary promising results by blocking tumor growth and inducing tumor regressions:

 

·         MK-0456 (VX-680 - a pyrimidine derivative)

·         AZD1152-HQPA (a quinazoline prodrug)

·         PHA-739358 (a pan-aurora (A, B, and C) inhibitor)

·         MLN8054 (the first orally available aurora kinase inhibitor and the first aurora A–selective inhibitor to enter human clinical trials)

 

These are just a few however other aurora kinase inhibitors are emerging and only further studies will tell which are most effective and warrant further clinical investigation for use in mesothelioma treatments. The significance and effectiveness of aurora kinases as anticancer targets is yet to be established in ongoing clinical trials. Further research is needed, yet initial results give hope that this may be helpful in the treatment of mesothelioma.