Chromosomal Instability: Biomarker for Predicting Response to Paclitaxel in Breast Cancer?

By: Hope Craig, MSPH
Posted: Friday, February 11, 2022

A study published in Science Translational Medicine may offer a major step forward in understanding the varying effects of paclitaxel on patients with breast cancer. By analyzing patient samples, Beth A. Weaver, PhD, of the University of Wisconsin-Madison, and colleagues focused on how paclitaxel may induce chromosomal instability, which may sensitize breast tumors to multipolar divisions. Chromosomal instability was found in about half of breast cancers in this study and may help identify which patients may be most likely to respond to paclitaxel.

“What we’re really trying to do is turn this conventional chemotherapy into personalized medicine,” Dr. Weaver said in an institutional press release. “That would be the best of all worlds, because paclitaxel is widely used, it’s inexpensive, and clinicians have a ton of experience with it.”

The researchers analyzed tissue samples of patients with breast cancer as part of a clinical trial to explore paclitaxel’s mechanism of action. They found that paclitaxel increased cell division with chromosome mis-segregation to induce cytotoxicity. Patients with high rates of chromosomal instability tended to be more sensitive to paclitaxel and seemed to have better tumor suppression. Both genetic and pharmacologic means of inducing chromosomal instability seemed to increase the efficacy of paclitaxel.

“Together, these results support the use of baseline rates of chromosomal instability as a predictive biomarker for paclitaxel response. Furthermore, they suggest that agents that increase chromosomal instability or maintain multipolar spindles throughout mitosis will improve the clinical utility of paclitaxel,” the authors commented.

Disclosure: Full disclosures of study authors are available at science.org.

Science Translational Medicine

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