In a study presented this month at the San Antonio Breast Cancer Conference, Drs. Mark Burkard and Beth A. Weaver of the UW Carbone Cancer Center showed that Taxol helps kill cancer cells by increasing the number of “mistakes” the rapidly dividing cells make as they replicate. The study showed that the drug works by increasing chromosomal instability (CIN). And while some tumors lack CIN, those that have low but non-lethal levels of instability are more likely to be killed off by Taxol.
“While Taxol has been one of our most effective therapies for breast cancer, we haven’t understood why about half of patients do not benefit,” says Burkard, a breast-cancer oncologist and researcher. “Our results suggest chromosomal instability may be an effective biomarker to predict which women will benefit from taxane therapy.”
Taxanes were discovered in the 1970s in the bark the yew tree, and it is currently manufactured from a compound found in yew needles. Taxane medications are some of the most widely used drugs for breast, ovarian and some other cancers.
Researchers performed chromosome analysis on 354 human breast cancers and found that 77 percent had greater than baseline amounts of CIN. They found higher rates of CIN in triple negative breast cancer (TNBC) and in cancers that were positive for human epidermal growth factor receptor 2 (HER2+) compared to other subtypes.
In previous work, they treated five women with Taxol and then biopsied their tumors 20 hours after the treatment. They were able to capture cancer cells undergoing abnormal divisions in the tumors, divisions that would cause chromosomes to be added or deleted, which would be more likely to destroy cancer cells that already have problems dividing normally.
The authors recently received a grant from the Department of Defense Breast Cancer Research Program to test if they can predict which patients will benefit from Taxol therapy. Burkard, an associate professor of medicine, says that if CIN does prove to be the best way to predict Taxol response, this finding could have a major effect on the way breast cancer is treated.
Other UW Carbone Cancer Center scientists involved in the study were Dr. Ludimila Cavalcante, Ryan Denu, and Lauren Zasadil. The study was supported by the UW Carbone Cancer Center, and by a National Cancer Institute R01CA140458 grant to Dr. Weaver.
University of Wisconsin School of Medicine and Public Health