Triple-Therapy Cocktail Shrinks Triple-Negative Breast Cancer Tumors

In a new study using mice and lab-grown human cells, a team of scientists led by Johns Hopkins Kimmel Cancer Center, the team found out that a triple-drug cocktail can shrink triple-negative breast cancer tumors by killing off cancer cells and halting the growth of a new tumor.

The Study

The combined treatment which was described in a paper published in the April 1st, 2016 issue of Cancer Research, is composed of the chemotherapy drug doxorubicin, all-trans retinoic acid or ATRA, and it can cause a tumor to lose its self-renewing cells. Entinostat makes cancer cells more sensitive to retinoic acid treatment.

Dr. Saraswati Sukumar, Ph.D., and a professor at the Johns Hopkins Kimmel Cancer Center, led the team and reports that EAD therapy, named for each of the drugs used in the combo, “significantly” reduces the size of triple-negative breast cancer tumors in mice and the number of lab-grown spheres of metastatic breast cancer cells harvested from patients and grown in the laboratory.
Sukumar and her team tested several pairings of drugs before determining that the EAD combination was the most beneficial against triple-negative breast cancer tumors. Doxorubicin alone was able to reduce the formation of tumor spheres grown in the lab by 32 percent, while entinostat alone or ATRA alone, could only reduce them by 18 percent. However, the combination EAD therapy reduced the formation of spheres by 90 percent.

Triple-negative cancers account for approximately 15 to 20 percent of all breast cancers. This type of cancer is named so because they test negative for, or lack, estrogen and progesterone receptors and the HER2 protein, all of which are implicated in other types of breast cancer. Without hormonal or HER2 receptors to target, patients with aggressive triple-negative breast cancers aren’t likely to respond to medications which target those molecules, said Sukumar. Combination chemotherapy drugs are the current standard of treatment for patients, but about one-quarter with triple-negative breast cancer will not respond to them. Thus, Sukumar states, finding combinations that work better than those in common use is an ongoing endeavor.

Previous research has shown retinoic acid drugs such as ATRA can rid breast cancer stem cells of their ability to multiply or self-renew and develop into more differentiated, mature breast cancer cells. When tumor cells lose their ability to self-renew through stem cells, they have less of a chance to grow and become invasive, says Vanessa Merino, Ph.D. a research associate at Johns Hopkins University School of Medicine, stem cell expert and study co-author.

Conclusion:

Dr. Merino states, “If the cancer is supplied with agents that can cause differentiation faster than their production, the tumor will shrink, since more cells are dying than are being produced to replace the dead ones.”
Sukumar says the next logical step for the triple-negative therapy would be to test its safety and effectiveness in patients with triple-negative breast cancers.

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