toothpick unappreciative: Combination Therapy For Breast Cancer Shows Promise

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology
Article Date: 05 Jul 2012 ? 13:00 PDT

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A study published in the July issue of Anticancer Research reveals that scientists from Boston University School of Medicine (BUSM) have found an effective combination therapy for breast cancer cells in vitro that can potentially be used for treating different forms of breast cancer, including cancers resistant to chemotherapy as well as other treatments.

The Centers for Disease Control and Prevention state that aside from non-melanoma skin cancer, breast cancer is the most common form of cancer amongst women in the U.S., and it is also one of the top mortality causes in women of all races.

About 14 to 20% of all breast cancer cases are triple negative breast cancer, meaning the cancer cells lack hormone receptors, including the HER-2 receptor, and are generally unresponsive to hormone and herceptin-based therapies. Triple negative breast cancer is a more aggressive cancer with higher recurrence and mortality rates than other types of breast cancer. This type of cancer is more prevalent in African-American women.

Study author Sibaji Sarkar, PhD, adjunct instructor of medicine at BUSM explains:

?Cancer is like a car without brakes. Cell growth speeds up and it doesn?t stop. When expressed, tumor suppressor genes, which work in a protective way to limit tumor growth, function as the brakes. They are not expressed in most cancers, causing the cancer to grow and potentially metastasize.?

The main aim in the development of anti-cancer drugs is to find a method to re-express tumor suppressor genes that can help to block the growth of cancer cells. Whilst some tumor suppressor genes are imprinted, i.e. only one of the genes inherited from the mother and father is functional, in those with cancer, both imprinted tumor suppressor genes can become non-functional and unable to stop tumor growth.

The researchers conducted an in vitro study to test a combination therapy of an epigenetic drug combined with a protease inhibitor on breast cancer cell lines that are hormone responsive and on those, i.e. the triple negative that are hormone unresponsive.

They used histone deacetylases inhibitors (HDACi) and calpeptin. Calpeptin blocks the protein calpain, which is involved in controlling signaling proteins and which is currently being researched as a potential treatment model for blood clots and other neurological diseases.

The researchers discovered that the combination therapy not only blocked cell growth, it also increased cell death in both cancer cell lines by inducing cell death and stopping the cell cycle. The dynamics in which the combination therapy inhibits cells growth was different. Unlike to the non-hormone responsive cells, the cells in the hormone responsive line inhibited the cell cycle at an earlier stage. In the triple negative breast cancer cell line, the inhibitors allowed ARHI, an imprinted tumor suppressing gene to re-express, which assisted in stopping the growth of cancer cells, leading to cancer cell death.

Sarkar, who is also a faculty member at the Genome Science Institute at Boston University says:

?The study data demonstrates that HDACi?s bring back the brakes of the car, halting cell growth and promoting cell death. These results provide a model to investigate the re-expression of tumor suppressor genes, including imprinted genes, in many forms of breast cancer.?

In conclusion, the study requires further investigation. However, it raises the chances of using this combination therapy for various types of breast cancers, including those that develop drug resistance to standard chemotherapies and those that are hormone refractory.

Written by Petra Rattue

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Source: http://cancerkick.com/2012/07/05/combination-therapy-for-breast-cancer-shows-promise/

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