Aggressive breast cancers may be sensitive to drugs clogging their waste disposal

In a new paper in Cancer Cell, a team led by Judy Lieberman, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine reports “triple-negative” breast cancers may be vulnerable to drugs that attack the proteasome. This cellular structure acts as the cell’s waste disposal, breaking down damaged or unneeded proteins.

These cancers, which lack the three major therapeutic markers for breast cancer - the estrogen, progesterone and HER2 receptors - are very aggressive and difficult to treat. They mostly affect younger women and have the worst prognosis of all breast cancers.

By selectively turning genes off throughout the genomes of triple-negative tumor cells in vitro, Lieberman’s team found that these cells absolutely require active proteasomes in order to live. When turned off, the cells die.

These data suggest that triple-negative breast cancers may respond to treatment with drugs similar to bortezomib (Velcade®), a proteasome inhibitor that revolutionized the care of patients with the blood cancer multiple myeloma.

The study was supported by the Department of Defense Breast Cancer Research Program, the National Cancer Institute (grant number R01CA146445) and the Breast Cancer Research Foundation.

Boston Children’s Hospital is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 13 members of the Institute of Medicine and 14 members of the Howard Hughes Medical Institute comprise Boston Children’s research community.

Aggressive breaSt cancers may be sensitive to drugs clogging their waste disposal Founded as a 20-bed hospital for children, Boston Children’s today is a 395-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Boston Children’s is also the primary pediatric teaching affiliate of Harvard Medical School.

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