In vitro study identifies potential combination therapy for breast cancer

July 2, 2012 in Cancer

A study conducted at Boston University School of Medicine (BUSM) demonstrates an effective combination therapy for breast cancer cells in vitro. The findings, published in the July 2012 issue of Anticancer Research, raise the possibility of using this type of combination therapy for different forms of breast cancer, including those that develop resistance to chemotherapy and other treatments.

The study was led by researchers at the Boston University Cancer Center. Sibaji Sarkar, PhD, adjunct instructor of medicine at BUSM, is the study's corresponding author.

According to the , breast cancer is the most common cancer among women in the United States aside from non-melanoma skin cancer. Breast cancer also is one of the leading causes of among women of all races and Hispanic origin populations.

Triple negative breast cancer, which accounts for approximately 14 to 20 percent of all breast cancer cases, is a type of the disease that occurs when the cancer cells lack , including the receptor called HER-2, and typically will not respond to hormone and herceptin-based therapies. Triple negative breast cancer occurs more often in African-American women and is considered to be a more aggressive form of the disease with higher rates of recurrence and mortality than other forms of breast cancer.

"Cancer is like a car without brakes. Cell growth speeds up and it doesn't stop," said Sarkar. "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."

A major focus in the area of anti-cancer drug development is to find a way to re-express tumor suppressor genes so that they can help inhibit . Some tumor suppressor genes are imprinted, meaning that from the two genes inherited from the mother and father, only one of the genes is functional. In cancer, both imprinted tumor suppressor genes may become non-functional and unable to stop tumor growth.

The researchers tested, in vitro, a of an epigenetic drug with a protease inhibitor on breast cancer cell lines that are hormone responsive and breast cancer lines, like triple negative, that are not hormone responsive. They utilized histone deacetylases inhibitors (HDACi) and calpeptin, which inhibits calpain, a protein involved in the regulation of signaling proteins. Calpain inhibition is being studied as a potential treatment model for blood clots and other neurological diseases.

In this study, they found that the combination therapy both inhibited cell growth and increased cell death in both cancer cell lines by inducing cell cycle arrest and cell death. However, the mechanism of how the combination therapy stops the cells from growing was different. Cells in the hormone responsive line stopped the cell cycle in an earlier phase compared to the non-hormone responsive cells. In the triple negative breast cancer cell line, the inhibitors allowed an imprinted tumor suppressing gene, ARHI, to re-express, which helped stop the growth of the cancer and led to cancer cell death.

"The study data demonstrates that HDACi's bring back the brakes of the car, halting cell growth and promoting cell death," added Sarkar, who also is a faculty member at the Genome Science Institute at Boston University. "These results provide a model to investigate the re-expression of , including imprinted genes, in many forms of ."

This study needs further investigation but raises the possibility of using this type of combination therapy for diverse types of breast cancers including those that are hormone refractory and develop drug resistance to conventional chemotherapy.

Provided by Boston University Medical Center search and more info website

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts

More news stories

New fluorescent tools for cancer diagnosis

In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...

Cancer created 19 hours ago | popularity not rated yet | comments 0

Modulating the immune system to combat metastatic cancer

Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...

Cancer created 19 hours ago | popularity 5 / 5 (1) | comments 0

Scientists put bowel cancer under the microscope

Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.

Cancer created 22 hours ago | popularity 5 / 5 (1) | comments 0

Researcher identifies breast cancer fighting hormone

Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.

Cancer created 23 hours ago | popularity 5 / 5 (2) | comments 0

Ground breaking cancer research finds immune system link

(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.

Cancer created 23 hours ago | popularity 5 / 5 (4) | comments 0


Feds fight morning-after pill age ruling in NY

(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...

Heart failure accelerates male 'menopause'

Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...

First drug to improve heart failure mortality in over a decade

Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...

Death highest in heart failure patients admitted in January, on Friday, and overnight

Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...

Engineered cytomegalovirus protects monkeys from HIV equivalent

(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...

Researchers identify first drug targets in childhood genetic tumor disorder

Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...