Approach to Personalizing Treatment of Triple-Negative Breast Cancer Shows Promise in Cell Lines – Michigan Medicine

Next, the team tested 78 approved or investigational cancer drugs against each of the cell lines, selecting the compounds based on their effectiveness in other solid-tumor cancers. After a series of initial experiments to gauge their effectiveness, 12 of the drugs were prioritized for deeper analysis.

Among these, the research group found six drugs that showed promising results against tumors with particular molecular features suggesting the approach is a solid first step toward developing robust biomarkers of drug response in triple-negative breast cancer.

Many other breast cancer subtypes are defined by the pathways that you would use to target them for example, youd treat HER2-positive breast cancer with a HER-2 inhibitor, says senior study author Sofia Merajver, M.D., Ph.D., a professor of internal medicine and epidemiology at the U-M. Triple-negative breast cancer is defined by its lack of hormone receptors and HER2 expression, which makes it much more difficult to target. We needed to do better.

Since cancer often quickly develops resistances against individual drugs, the researchers also wanted to use their multi-omic approach to look for ideal combinations of drugs.

The idea is that if we find a marker that is particularly high in drug-resistant cells, we might be able to make the cells more responsive to treatment by adding a drug that also targets that marker, says senior study author Matthew Soellner, Ph.D., an assistant professor of internal medicine and chemistry at U-M, and an affiliate faculty member of the U-M Life Sciences Institute. Ultimately, we found we could make most of the cell lines more sensitive to our target drug it worked better than we had hoped for.

The research was supported by the National Institutes of Health (1R21CA218498), the Breast Cancer Research Foundation, Tempting Tables, The Rose Run, and the Kathy Bruk Pearce Research Fund of the U-M Rogel Cancer Center.

Additional authors include Eric J. Lachacz, Nathalie M. Vandecan, Peter J. Ulintz, Liwei Bao, John P. Lloyd, Joel A. Yates and Aki Morikawa, all of U-M.

Paper cited: Molecular determinants of drug response in TNBC cell lines, Breast Cancer Research and Treatment. DOI: 10.1007/s10549-019-05473-9

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Approach to Personalizing Treatment of Triple-Negative Breast Cancer Shows Promise in Cell Lines - Michigan Medicine