Researchers identify potential target for treating triple-negative breast cancer

A team at the University of Kansas School of Medicine has identified a potential target for treating breast cancer, including a particularly deadly form of the disease.

So-called "triple-negative" breast cancer represents between 12 and 17 percent of all breast cancers. It derives its name from the lack of receptors for estrogen, progesterone and Her2. The absence of these receptors rules out proven hormone therapies such as tamoxifen. Triple-negative breast cancer can be more aggressive and is more likely to recur than other breast cancers.

Because of the lack of existing therapies, the KU team chose to examine a member of a family of protein kinase enzymes. In recent years, atypical protein kinase C signaling has been found in the tissue invasion and metastasis of multiple tumors.

The research team, including Soumen Paul, Ph.D., associate professor, Arindam Paul, Ph.D., assistant professor, and Ossama Tawfik, professor, M.D., Ph. D., all in the Department of Pathology and Laboratory Medicine, and their colleagues, studied atypical protein kinase c lambda/iota signaling during the invasive progression of triple-negative breast cancer. Among other tests, they looked at tissue samples of breast cancer that had spread to the liver, lung and other organs. They found that atypical protein kinase c lambda/iota, which is known to influence cell growth, was highly expressed and phosphorylated in metastatic breast cancers.

To further test the relationship, the researchers depleted the protein in a line of triple-negative breast cancer known to be highly invasive and metastatic. The tests, conducted in mice, found that depleting the protein significantly slowed the breast tumor growth.

Previous studies, Dr. Soumen Paul said, had implicated the atypical protein kinase c lambda/iota in the other carcinomas. But no prior study had indicated any role in breast cancer metastasis. In a recent paper, published in the journal Cell Death and Differentiation, Dr. Paul and his colleagues conclude that atypical protein kinase c lambda/iota holds "tremendous" promise for treating breast cancer.

"We have been able to show that this protein is highly expressed in metastatic triple-negative breast cancer, and when we are depleting it from triple-negative breast cancer cells, we found that the cancer cells are not metastasizing," Dr. Paul said. "The tumor growth is slowing down. This is giving us an opportunity for a targeted therapy."

Dr. Soumen Paul has worked with medicinal chemists to design analogues of a compound capable of inhibiting protein kinase c lambda/iota. "Targeting this protein might prevent metastasis and recurrence of breast cancer," Dr. Paul said.

He is the senior author of the paper and a member of the Institute for Reproductive Health and Regenerative Medicine and The University of Kansas Cancer Center.  Other members of the University of Kansas Cancer Center and the departments of Molecular and Integrative Physiology, Pathology and Laboratory Medicine, and Urology also contributed in this study.

The work is supported by NIH grants HD062546, HL094892 and HD075233. Co-author Pratik Home, Ph.D., is supported by a postdoctoral fellowship from American Heart Association. This work was also supported by a gift from Deffenbaugh Foundation and a grant from the Kansas Intellectual and Developmental Disabilities Research Center (HD002528) and Illumina to Dr. Arindam Paul.

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