Israel-US Team Kills Breast Cancer in the Dark

Article on Arutz Sheva June 12, 2009
By by Karin Kloosterman

With the alarming incidence of breast cancer in America -- one in eight women can expect to get it sometime in their life -- new solutions for women, their mothers, sisters, aunts, daughters and friends, cannot come fast enough. An Israeli-American research team has stumbled onto a new and interesting find - a non-radiation based therapy that may provide relief for an aggressive and hard to treat breast cancer cell known as HER2+, but which could also have wider applications for treating all kinds of cancer.

Breast cancer alone is the most common form of cancer among U.S. women, and the second leading cause of death after lung cancer. About 200,000 women in the U.S. alone had breast cancer in 2008, and about 40,000 will die from it each year.

Prof. Zeev Gross, from the Technion / Israel Institute of Technology has played no small role in the new research paper that shows positive results for the new non-radiation based therapy based on the chemical compound gallium corroles.

Published in the prestigious Proceedings of the National Academy of Sciences, the Israel-U.S. team, including scientists from the California Institute of Technology and the Cedars-Sinai Medical Center were able to show positive pre-clinical results on the new treatment that homes in on HER2+.

Using a new-to-science organic chemical called a corrole, described about 10 years ago, Gross was able to develop a powerful method that synthesizes these chemicals for practical use in medicine. From being able to make a couple of milligrams in two years, Gross' team could produce two grams in two days.

Lights up and kills cancer
The beauty of the new chemical compound, waiting for an investment in order to go to clinical trials, is that it not only works in diagnostics, lighting up and showing doctors where the cancer cells are, it is also somehow able to kill the cancer at the same time. Gross has also found it works for treating arterial sclerosis, or hardening of the arteries, which leads to heart disease.

"We started in cancer wanting to take advantage of a property of this compound," Gross tells ISRAEL21c. "They are highly florescent and we wanted to use them to detect cancer. We found at the cellular level [gallium corroles were] useful for imaging, but also found it could kill cancer with high specificity and could be an alternative to chemotherapy.

"We were surprised," he continues. "It could be used for selective killing of cancer cells. Focusing on breast cancer cells, our collaborators developed a vector, a virus based gene delivery protein, and we said let's use it for corroles."

Testing this idea, the researchers were pleased to see the dual effects of this chemical. Gross explains: "In most cases, if people want to get a closer look at a drug in vivo, they have to attach a fluorescent probe to it - and that turns it into a different molecule.

"But in our case, the active molecule we're tracking does the fluorescing. We get to track the original, unmodified molecule and are hence able to follow its distribution among different organs in live animals."

Fewer side effects than chemotherapy
In the new study the international team combined a gallium corrole with a protein carrier so that the corrole would show an affinity to cancer cells. According to the researchers, when tried on mice with breast cancer, it became a targeted cancer therapy able to both detect and eliminate tumors in mice. They report fewer side effects compared to other breast cancer treatments.

Corroles are similar in structure to porphyrin molecules used today in a well-researched cancer treatment called photodynamic therapy, or PDT. Porphyrin compounds are injected into the body and are then exposed to specific wavelengths of laser light. The light causes the porphyrins to create tumor-killing oxygen radicals.

The difference between porphyrins and the team's corroles, explain researchers, is that corroles don't need laser light to be activated, in effect it's killing "cancer cells in the dark," they say.

In the study on mice corroles, the Israel-U.S. team was able to shrink breast cancer tumors at doses five times lower than standard chemo treatments (based on a drug called doxorubicin). Also, the corroles could be injected straight into the bloodstream and not into the tumor, making the treatment, if developed clinically, easier to administer.

"Using lower concentrations means less toxicity. Doxorubicin tends to have significant heart toxicity; this therapy seems likely to be much less damaging to the heart," Daniel Farkas, a co-researcher in the study and the director of Cedar-Sinai's Minimally Invasive Surgical Technologies Institute tells ISRAEL21c.

Putting statins out of business?
But the Israeli team finds it could work in heart disease as well: iron corroles are also able to provide reversal effects of arterial sclerosis, or hardening of the arteries, says Gross. With a different mode of action than gallium corroles, "We took mice prone to develop arterial sclerosis and treated them with the same family of compounds. It's a very potent antioxidant," he says. "It's interfering with the process causing arterial sclerosis."

"We already know about green tea, red wine, or pomegranate," he explains, noting that his innovation is better than natural antioxidants that at same stage can also attack vital biomolecules. The therapy was shown to work in successful pre-clinical studies, while the medicinal value of corroles, says Gross, was something his Technion lab initiated 10 years ago.

"We discovered how to synthesize corroles and are the main people pushing forward the fundamentals of science," says Gross, noting the applications are wide and three-fold in catalysis, in medicine, and in renewable energy.

The Technion lab's senior scientist Dr. Atif Mahammed, an Israeli Arab is "a leading figure in this whole project," says Gross, who says his lab is also enriched with a team of gifted scientists from the former Soviet Union.

Funding for the research was provided by the United States-Israel Binational Science Foundation, the National Science Foundation in the US, the National Institutes of Health, the US Department of Defense, Susan G. Komen for the Cure, the Donna and Jesse Garber Award, the Gurwin Foundation, and the U.S. Navy Bureau of Medicine and Surgery.