GUMC Researchers Discover Potential Anti-Cancer Drugs

Georgetown University Medical Center researchers introduced a possible anti-cancer therapy in the form of two drugs sourced from the plant hormone strigolactone in a study published Feb. 16.

The two drugs have been found to cause DNA breakage and turn off a major DNA repair mechanism in cancer cells, thereby inhibiting the ability of more aggressive cancers to repair themselves once damaged.

The synthetic plant compounds, also known as MEB55 and ST362, have only recently been introduced into the realm of human health. Georgetown University Lombardi Comprehensive Cancer Center researcher and professor Ronit Yarden, along with a team of researchers, was the first to publish the role of strigolactones in mammalian rather than plant cells.

The team included researchers from Georgetown, the Agricultural Research Organization in Israel, the University of Turin in Italy, the National Cancer Institute and the Memorial Sloan Kettering Cancer Center.

In a previous study, Yarden and her team reported that strigolactones induce apoptosis, or programmed cell death, and cell cycle arrest. In this most recent study, Yarden and her team investigated the processes by which these agents cause cell death.

Cancer cells rely heavily on DNA repair mechanisms, which are necessary for cell survival. The two hormones studied were found to trigger a DNA damage-like response.

According to Preclinical Imaging Research Laboratory Director and founder Christopher Albanese, specific pressures are too much for cancer cells to handle, which leads to damaged DNA. Once DNA becomes damaged beyond repair, the cell will die.

“Cancer cells are very smart, smarter than us. Certain stresses, though, are too much for them to handle, like damaged DNA,” Albanese said. “The hormones in the study induced a DNA damage-like response, which leads to inevitable cell death mode. The hope is that cancer will be become much more manageable.”

The researchers found that strigolactones halt the DNA repair process after the cell’s DNA is copied and before it divides. However, even if one repair mechanism is shut down, the cancer cells have the capacity to rely on a second repair mechanism and still survive.

The team is currently experimenting with the compound in mice studies. If the mice studies are successful, the drug will move to a phased clinical trial. The researchers hope to eventually begin testing on humans, and ultimately receive a drug company investment in their compound.

Yarden said she conceived the idea of using plant compounds to combat cancer cells in an unconventional way.

“It was very random. I have a friend, who is now my collaborator, and she is a molecular biologist but of plants. We discussed our research at a social event and she told me she was working with those compounds and that they have some properties that inhibit cell cycle and stem cells in plants,” Yarden said. “It was a long shot, a very long shot. We thought that if they inhibit stem cells in plants, maybe these universal systems would also be applicable for cancer cells.”

Though the study initially focused on breast cancer, Yarden said she soon realized the compounds could battle other types of cancers as well.

“We started with breast cancer because that was my main research before this project, but now we have tested many different cancer cell lines and we know that it’s effective toward prostate, lung and color cancer cell lines,” Yarden said. “In both prostate and breast cancer we noticed that it’s very effective toward the more aggressive types of cancer cells.”

Albanese said the hope is if these drugs are applied to humans, the same therapeutic activity will occur.

Albanese highlighted the important role of drug companies in drug research, saying that corporations are primarily interested in investing in certain drugs that will have large payoffs.

“Drug companies need to see that the drugs in vivo work with the same mechanisms as in cell culture,” Albanese said. “In order to get a drug to market, you need money and interest. Drug companies are looking for blockbuster drugs to pay for expenses.”

Albanese added that the drugs are a long way from going on the market, in part because of the high costs of putting a drug through the process of obtaining U.S. Food and Drug Administration approval.

“The failure rates are huge, the costs are even more huge,” Albanese said. “It takes up to one billion dollars to get from the stage we are at now to FDA approval.”

The research primarily focused on breast cancer, but the team also tested many different cell lines, including prostate and colon cancer cells. In prostate and breast cancer, the drugs were more effective against the more aggressive types of cancer cells.

Yarden stressed that because the drug is in such an early stage, the researchers cannot guarantee the drug’s ability to fully treat cancer.

“It’s a long way. We just started the studies in May,” Yarden said. “It’s just such an early phase.”

Jefferson Haake (NHS ’16), one of the primary researchers published in the study, said that despite the strigolatones’ aggression toward cancer cells, they do not harm normal cells, which is a problem often associated with chemotherapy treatments. Haake added that the lack of damage inflicted on normal cells could alleviate the side effects that typically accompany anti-cancer therapeutic treatments. This would allow a higher dosage of drugs in chemotherapeutic regimens and enable a more aggressive attack on the cancer cells.

“The two main takeaways from this study for the educated layperson are that, the compound is something that is toxic toward cancer but not to, as far as we know, non-cancer cells,” Haake said. “You are actually killing the cancer as opposed to getting your own cells caught in the crossfire. That’s a big issue with chemotherapy today, is that you are essentially pumping someone full of toxins and hoping that it takes the cancer faster than it takes the person.”

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