Drexel duo developing drug to stop cancers' spread

Alessandro Fatatis (left), a cancer biologist, and Joseph M. Salvino, a medicinal chemist, won a coveted spot in the National Cancer Institute's Experimental Therapeutics Program.
Alessandro Fatatis (left), a cancer biologist, and Joseph M. Salvino, a medicinal chemist, won a coveted spot in the National Cancer Institute's Experimental Therapeutics Program. (JIM GREIPP)
Posted: August 18, 2014

Like many new relationships, this one developed over a cup of coffee. Except this one might lead to a new drug to inhibit the spread of cancer cells.

Joseph M. Salvino, a medicinal chemist, and Alessandro Fatatis, a cancer biologist, crossed paths in spring 2010 at a departmental meeting at the Drexel University College of Medicine.

Fatatis presented his recent discovery that breast and prostate cancer cells possess a receptor that allows them to infiltrate the bone, often the first site of metastasis for these cancers.

When the coffee came out, Salvino approached Fatatis, and the researchers discussed how the discovery could be turned into a treatment. Fatatis, who presented his research with a thick Italian accent, challenged the goatee-sporting Salvino to create a small molecule to block the crucial receptor. Two weeks later, the chemist showed up at Fatatis' office with a vial of powder.

Now, the duo have developed an improved version of their compound, which they hope will eventually prevent the cancers from spreading further once they have metastasized. And because it only blocks cancer cells from landing at their intended targets - it doesn't kill any cells, cancerous or not - the substance in theory is nontoxic.

"It wasn't just luck," said Fatatis, who worked with Salvino for two years to develop the compound, which worked in mice. They had probably a hundred meetings, brainstorming ways to improve its design. They named their most promising version JMS17-2 after Salvino. In May last year, they were awarded a U.S. patent for the cancer-fighting abilities of their approach.

Then in March, their bench-to-bedside collaboration won them a coveted spot in the National Cancer Institute's Experimental Therapeutics Program.

The program develops promising anticancer drugs. Rather than handing out grants, it provides access to the institute's vast resources and subcontracts drug-development work to institutions around the country.

If all goes well, clinical trials for women with advanced breast cancer could begin in three to five years.

The next step is to fine-tune this compound, making sure it isn't cleared from the body too rapidly and doesn't interact with other drugs.

When breast and prostate cancer cells leave their tumorous home, they circulate in the blood until they come upon a protein called fractalkine on the cells lining the bone marrow. (Fatatis' interest in this protein came from another Drexel collaborator, neuroscientist Olimpia Meucci, who is also his wife.)

Once the cancer cells find fractalkine, their receptors - known to exist on other types of cells but not breast and prostate cancer until Fatatis' discovery - bind tightly to the protein. Chemical signals then lure the cells into the bone, where they form new tumors.

The new compound works by latching onto the cancer cells' receptors, preventing them from binding to the bone-based fractalkine. Without a new home, the cancer cells wander around in the bloodstream and die within 48 hours, said Fatatis.

This potential drug prevents the "reseeding" of tumor cells, he said. At diagnosis, breast and prostate cancer cells may have already spread. The goal is to stop them from reaching other sites in the bone and spreading to organs such as the brain and liver, where they can kill.

The researchers hope their drug can be taken orally, alongside chemotherapy. This type of combination therapy can be especially useful after tumors are surgically removed, when the risk of metastasis is high, Fatatis said. Salvino envisions patients' staying on the drug for the long term after their other treatments end.

But even effective drugs can cause harm. It's far too early to say that the compound won't have adverse effects in the long run, said Charu Aggarwal, an assistant professor of medicine at the University of Pennsylvania. Aggarwal, who studies circulating tumor cells, thinks the Drexel work is "interesting and exciting," but has concerns.

The same receptor that appears on breast and prostate cancer cells is also present on white blood cells, which protect the body from infection and disease. Blocking those receptors could dampen an immune system already weakened by cancer.

Fatatis has not seen this side effect in animal studies, but the researchers will be looking for it in human trials. "Until we try," he said, "we won't know."


rachel.zamzow@gmail.com

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