The inhibition of two proteins involved in cell division increases the sensitivity of cancer cells to the widely-used anticancer drug taxol. Researchers from the University Medical Center (UMC) Utrecht demonstrate this in their article published in the online version of the PNAS journal dated October 23, 2009. This finding could lead to more effective chemotherapy using taxol.
Doctoral candidate Aniek Janssen has conducted research on two proteins (Mps1 and BubR1) that are involved in cell division. Inhibiting these proteins results in the delay of cell division because the replicated DNA is not evenly distributed over the new cells. The commonly used anticancer drug taxol blocks cell division using a similar strategy but its effectiveness is limited.
The researchers from UMC Utrecht have now demonstrated that combined therapy involving a low dosage of taxol and the gradual deactivation of the cell-dividing proteins Mps1 or BubR1 results in more tumor cells dying off. This increase in cell death does not occur in healthy cells. Chemotherapy with taxol could therefore be both more effective and more tumor-specific when given in combination with Mps1 or BubR1 inhibitors. Unfortunately such inhibitors do not yet exist.
Janssen conducted her experiments mainly with human cancer cell lines. Through so-called RNA interference she was able to switch either Mps1 or BubR1 (the proteins involved in cell division) and subsequently analyze the sensitivity to taxol. However, although this method is suitable for demonstrating how proteins function in cell lines, the findings cannot be transferred directly to the clinical setting. Therefore, drugs need to be developed that specifically inhibit these proteins that drive cell division. Worldwide, many pharmaceutical companies are trying to develop such a drug.
Doctors use taxol widely, and it is known to be effective in the treatment of lung cancer, ovarian cancer and breast cancer etc. The drug hinders cell division and therefore prevents tumor growth. Treatment with taxol does, however, require careful adjustment of the dosage so that the correct level is attained. For example, sometimes taxol only works when high doses are given but this is often accompanied by severe side effects such as problems with blood formation and neurological problems.
The study was conducted at the Cancer Center at UMC Utrecht and was led by René Medema from the Department of Medical Oncology.