Researchers find drug combination to reverse drug resistance in breast cancer

Scientists belonging to the University of Notre Dame have modeled the potential drug resistance of a breast cancer tumor using a novel method for genetic profiling of individual cells, and have successfully identified a drug combination that can reverse the resistance. Siyuan Zhang, Dee Associate Professor, Biological Sciences, Notre Dame, and his team employed a new profiling system, known as high-throughput single-cell profiling, to make the discovery and his lab collaborated with the University’s Genomics and Bioinformatics Core Facility to apply the same on campus. The team’s findings have been published in the journal Nature Communications.

For a long time, patterns of gene expression for cancer tissue have been found by using whole tumor tissue in a process dubbed bulk sequencing. However, cancer cells are entangled in a matrix of other cells, which makes it challenging to distinguish the individual cells. In this research, the team examines the mechanism of the drug CDK 4/6 inhibitor, used for blocking a particular type of enzyme, to study how it shrinks tumors in HER2 positive breast cancer. The drug works rapidly, and by the time the researchers could collect any data, it had shifted to something else. Zhang and his team then ran tests alongside the clinical trial for the CDK 4/6 drug, and by using the single-cell profiling technology, they discovered a type of tumor-infiltrating immune-suppressive cells that caused the resistance. When the team added a second FDA-approved drug to target the immune-suppressive cells, they found that the combination undid the resistance.

Zhang says that the new combination of drugs indicates that the drug-resistance in tumors can be treated and can also maintain and regulate the tumor size for an extended period. Considering the effectiveness of the supplement drug, Zhang believes clinicians could incorporate the combination therapy before any sign of resistance. Michael Pfrender, Director, Genomics and Bioinformatics Core Facility and Professor, Department of Biological Sciences, states that single-cell profiling could lead to further discoveries.


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