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Popular Chemo Drug Not Working as Experts Thought, UW Study Finds

Madison, Wisconsin - Taxol, the best chemotherapy drug for breast cancer, seems to shrink only about half of the tumors treated. What’s more, it doesn’t seem to work the way most thought, so how can doctors make an informed decision about which patients can benefit from the drug?


According to a study by University of Wisconsin-Madison scientists, shrinking tumors had more to do with how chromosomes were divided instead of the drug’s intended goal, stopping cell division (mitosis) altogether. With new results in hand, researchers hope to identify patients who will respond well to the drug.


Taxol, also known as paclitaxel, has been around since the 1980s, but scientists thought the drug prevented cells from dividing.


As the cell prepares to divide, its chromosomes are pulled in opposite directions by microtubules until the chromosomes separate. Once the genetic material is separated to different ends of the cell, nuclei form in the cell around the chromosomes, and the cell splits into two daughter cells.


“Normally, cells should divide their chromosomes in two directions, but with Taxol, they are dividing their chromosomes in three, four, or even five different directions,” said Dr. Beth Weaver, assistant professor of cell and regenerative biology.


Ultimately, two or three new cells are still formed, but the chromosomes are out of place or missing, causing a significant amount of chromosome missegregation. That condition often leads to cell death, according to the study published in the journal Science Translational Medicine.


“We asked some of our patients to volunteer and help us with our study,” said Dr. Mark Burkard, medical oncologist and member of the UW Carbone Cancer Center. “We had a number of patients who were kind enough to volunteer a biopsy that they wouldn’t have otherwise had to do so we could study how the drug was affecting the cancer in the breast.”


Working in the first tower of the Wisconsin Institutes for Medical Research, Burkard and Weaver were able to compare how much a tumor shrank in the patient to how cells from the biopsy were responding to the Taxol. In some cases the tumors shrank a lot, and in some cases it didn’t shrink at all, which was expected.


“The really interesting thing was that the shrinking tumors didn’t have a lot of cells get stuck during cell division. Most scientists previously thought that if the cells got stuck in the process because of the drug, then the tumors would shrink. But that wasn’t the case at all,” said Burkard.


Together, they hope to understand how they can use this new information to determine which tumors will respond to the drug. Based on some of the research being done by Weaver’s lab, some cancers are already using abnormal processes during cell division, and Taxol may be making it harder for the tumor cells to divide.


“Even though this initial sample size was small, this has completely changed the way we think about a drug that we’ve been using for 30 years,” said Weaver. “It goes to show that just a small number of patients can make a dramatic change.”


The next step for Weaver and Burkard is a retrospective study of several hundred patients who’ve received Taxol for other cancers. By analyzing test results, tumor measurements before and after treatment, and tumor samples from these patients, they hope to confirm a biomarker that could predict tumor shrinkage.

Date Published: 04/03/2014

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Popular Chemo Drug Not Working as Experts Thought, UW Study Finds

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