Tags: Cancer | triple-therapy | cocktail | shrinks | triple-negative | breast | tumors

Triple-Therapy Cocktail Shrinks Triple-Negative Breast Tumors

Triple-Therapy Cocktail Shrinks Triple-Negative Breast Tumors
(Copyright AP)

Friday, 20 May 2016 12:47 PM


Triple-negative breast cancer accounts for up to 20 percent of all breast cancers, and is difficult to treat because it is aggressive and does not respond to many conventional therapies. But a study at Johns Hopkins Kimmel Cancer center using mice and lab-grown human cells found that a triple-drug cocktail called EAD can kill existing cancer cells and stop new tumor growth.

EAD therapy consists of three drugs included in the treatment: chemotherapy drug doxorubicin; all-trans retinoic acid, or ATRA, which can cause a tumor to lose its self-renewing cells; and entinostat, which makes cancer cells more sensitive to retinoic acid treatment.

Saraswati Sukumar, Ph.D. and her colleagues tested several combinations of drugs before determining that the EAD grouping was the most potent against triple-negative tumors. For instance, doxorubicin alone was able to reduce the formation of tumor spheres grown in the laboratory by 32 percent, while entinostat alone or ATRA alone could reduce them only by 18 percent. However, the combination EAD therapy reduced the formation of spheres by 90 percent.

Compared to the combination of entinostat and doxorubicin, EAD reduced by twofold the number of tumor-starting cells in the tumor spheres, suggesting that the addition of ATRA helped to move the tumor away from a "stem-like" state to a more differentiated group of cells that are more responsive to drugs.

In spheres grown from six patients' metastatic triple-negative breast cancer cells, EAD was also the most effective at decreasing tumor growth, reducing the number of spheres formed by about 80 percent, compared to about 40 percent reduction by the next-best treatment of doxorubicin alone.

Previous research showed that retinoic acid drugs such as ATRA can eliminate the ability of breast cancer stem cells to multiply and develop into more differentiated, mature breast cells. When tumor cells lose their ability for self-renewal through stem cells, they are less likely to grow and become invasive, says Vanessa Merino, Ph.D., co-author of the study.

"If the cancer is supplied with agents that can cause their differentiation faster than their production, the tumor will shrink, since more cells are dying than are being produced to replace the dead ones," she says.

The next step will be to test the triple therapy on human patients with triple-negative breast cancer.


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Health-News
Triple-negative breast cancer accounts for up to 20 percent of all breast cancers, and is difficult to treat because it is aggressive and does not respond to many conventional therapies. But a study at Johns Hopkins Kimmel Cancer center using mice and lab-grown human cells...
triple-therapy, cocktail, shrinks, triple-negative, breast, tumors
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2016-47-20
Friday, 20 May 2016 12:47 PM
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