Drugs targeting gene activity fight chemotherapy resistance

By Paul Basilio, MDLinx
Published October 11, 2017

Key Takeaways

New research published in the journal Cell Metabolism has revealed potential treatment targets for patients with triple-negative breast cancer. The research was conducted at the Vanderbilt-Ingram Cancer Center and was led by Carlos Arteaga, MD, now the Director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.  

The findings showed that resistance to chemotherapy is associated with increased activity of the genes MCL1 and MYC. The increased activity boosts mitochondrial oxidative phosphorylation, which promotes the growth of chemotherapy-resistant cancer stem cells.

“Alterations in these two genes are easily detectable with tumor gene tests in current use,” said Dr. Arteaga, who is also Professor of Internal Medicine at UT Southwestern Medical Center. “Combinations of drugs that inhibit MCL1 or MYC  or both, have the potential to reduce the development of chemotherapy resistance and should be studied in clinical trials.”

While most breast cancers can be treated with hormone therapy, approximately 15% are triple-negative cancers with cancer cells not influenced by hormones, such as estrogen or progesterone. These types of cancers must be treated with chemotherapy, which can often be toxic to both cancer cells and healthy cells.

In addition, most triple-negative breast cancers eventually become resistant to chemotherapy, leaving the cancer to spread unchecked.

Dr. Arteaga, who holds The Lisa K. Simmons Distinguished Chair in Comprehensive Oncology, states that drugs that inhibit activity of MCL1 or MYC are currently in development. In conjunction with standard chemotherapies, these drugs have the potential to slow, or even prevent, the development of chemotherapy resistance.  

Research was supported by the Susan G. Komen for the Cure Foundation, the Breast Cancer Research Foundation, a National Institutes of Health Breast Cancer SPORE grant, and a Vanderbilt-Ingram Cancer Center Support Grant.

To read more about this study, click here

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