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AUB cancer breakthrough in mice raises hopes for humans

File - First lady Wafaa Sleiman, center, attends the 12th annual national breast cancer awareness campaign at AUB in Beirut, Saturday, Oct. 5, 2013. (The Daily Star/Dalati Nohra, HO)

BEIRUT: Lebanese scientists have tested a drug developed here that successfully treats an aggressive form of breast cancer in mice, in a potential early breakthrough in the disease’s treatment.

The drug is still years away from being tested on humans and commercially produced, but if proven safe through clinical trials, it could be used to fight advanced breast cancer tumors while sparing healthy living cells.

It works by targeting a protein common in late-stage tumors, prompting cancer cells to self-destruct and preventing the cancer from spreading to other organs.

The drug showed promising results against cancer cells in petri dishes and lab mice. About half of the mice that were given the drug after being injected with cancer cells survived beyond 60 days. Over the same period of time, 90 percent of the mice who were not given the treatment died.

“We were amazed by the increased survival of the treated mice,” said Khaled Ghattass, the lead author of the study who recently completed a doctorate in cell and molecular biology at the American University of Beirut. “We did not expect that it would have such an impact.”

Breast cancer is the most common type of cancer among women in Lebanon. The Public Health Ministry estimates that about 40 percent of cancer cases in women are breast cancer, with around half of those cases under the age of 50.

The drug, which is called DCQ, acts against cancer cells in an environment with limited oxygen, a state known as “tumor hypoxia,” which is characteristic of more aggressive strains of breast cancer.

It was synthesized in the lab of Makhlouf Haddadin and tested in the labs of Hala Gali-Muhtasib and Marwan al-Sabban, all professors at the American University of Beirut. The reaction that synthesizes the drug is called the Beirut Reaction and was developed and patented by Haddadin.

The drug only works in this oxygen-deprived environment and targets a particular protein that is crucial to cancer cell reproduction, triggering a process called “apoptosis,” or cell suicide.

Normal tissues and cells in the body are usually not oxygen-deprived, so they are not affected by the drug.

Hypoxia is also associated with the growth of cancer stem cells, which allow the tumor to grow in size and regenerate. It is also linked to “metastasis,” or the spread of cancer cells from, for example, the breasts to the liver or lungs.

This means that hypoxia is usually a feature of advanced cancers, where chemotherapy is not effective.

The researchers, all of them from AUB, tested the drug first on three strains of breast cancer cells in a petri dish and then on mice.

The results of the experiment were published in Molecular Cancer, an international peer-reviewed medical journal, late last month.

DCQ managed to block the growth of the cancer cells in the petri dish.

After that, Ghattas injected mice with the more dangerous strain of cancer cells, which can spread from the breast to other organs. Some of the mice were treated with the DCQ drug, and the growth of the tumor was monitored on a weekly basis.

Three weeks after treatment, the tumor growth was found to be greatly reduced by DCQ, and around half of the mice survived beyond two months after being injected with the cancer. The majority of the mice who were not treated with DCQ had died by that time.

DCQ was successful in preventing the spread of cancer in mice from the breast to the liver and lungs. This “metastasis” is the most common cause of death in individuals with breast cancer.

The fact that DCQ acts at such an advanced stage raises hopes in the possibility of treating advanced breast cancer, which becomes harder to defeat after a late diagnosis.

The scientists believe that DCQ works by targeting a protein called HIF-1 alpha. In normal cells with abundant oxygen, the protein degrades and does not build up in the cell. In babies in the womb, HIF-1 alpha is necessary in the formation of specialized cells, like liver cells and cartilage.

But if the cell is deprived of oxygen, such as in breast cancer, it accumulates and copies gene patterns that are linked to the spread of breast cancer to the rest of the body.

HIF-1 alpha also makes the breast cancer cells resistant to treatment.

By targeting HIF-1 alpha, the drug triggers “apoptosis,” a process of programmed cell death that kills the cancer cells.

Ghattass, who now works for a company in Saudi Arabia that specializes in conducting clinical research on new drugs for humans, said he would definitely consider proposing the testing of the drug on humans after carrying out additional tests that would determine the drug’s efficacy and toxicity.

The process from first identifying a potential treatment, to human trials and eventually putting the drug on the market can take over a decade.

But Ghattass hopes the drug could eventually prove to be a breakthrough in breast cancer treatment. Such treatment would be a ray of hope for millions of breast cancer patients worldwide.

 
A version of this article appeared in the print edition of The Daily Star on February 08, 2014, on page 3.

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Summary

Lebanese scientists have tested a drug developed here that successfully treats an aggressive form of breast cancer in mice, in a potential early breakthrough in the disease's treatment.

About half of the mice that were given the drug after being injected with cancer cells survived beyond 60 days. Over the same period of time, 90 percent of the mice who were not given the treatment died.

The researchers, all of them from AUB, tested the drug first on three strains of breast cancer cells in a petri dish and then on mice.

After that, Ghattas injected mice with the more dangerous strain of cancer cells, which can spread from the breast to other organs. Some of the mice were treated with the DCQ drug, and the growth of the tumor was monitored on a weekly basis.

Three weeks after treatment, the tumor growth was found to be greatly reduced by DCQ, and around half of the mice survived beyond two months after being injected with the cancer.

HIF-1 alpha also makes the breast cancer cells resistant to treatment.


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