These molecules interfere with the normal completion of cell division (mitosis) and have potential for further development as cancer therapeutics.
The study is published in the October 15, 2012 issue of The Journal of Cell Biology.
In previous work, senior study author Jonathan Higgins, PhD, Division of Rheumatology, Immunology and Allergy, BWH Department of Medicine, and colleagues found that Haspin must be present in cells for another protein, Aurora B, to be localized normally during cell division. Aurora B is a kinase required for accurate chromosome segregation in mitosis.
In this new study, Higgins’ team developed drug-like molecules that can enter cells and inhibit the activity of Haspin, causing the mislocalization of Aurora B and a failure of normal cell division.
Anti-mitotic drugs that inhibit cell division are commonly used in cancer therapy, and a number of new such drugs have been developed and are in clinical trials with the hope that they lack some of the side effects of current agents.
Haspin inhibitors represent a new class of anti-mitotics that have shown anti-tumor activity in pre-clinical models. The researchers state that further testing of the anti-cancer properties of Haspin inhibitors is still needed, including work to determine if they are more effective in combination with existing drugs.
This research was supported by the National Institutes of Health (R01CA122608, R01GM074210, R01GM50412), the Association for International Cancer Research, the Leukemia and Lymphoma Society Scholar Award, and the McCasland Foundation.