Dr. Horwitz is working on a new anti-tumor agent to fight cancer.

A drug-screening operation run by Wayne State University and the Karmanos Cancer Institute hopes to add another success story to its already impressive list.

In the last five years, the operation has identified six drugs that have passed the stringent FDA approval process and are now in use in the clinic, according to Jerome Horwitz, PhD, WSU professor of internal medicine and co-leader of the developmental therapeutics program at the Karmanos Cancer Institute. “Nationwide, there probably isn’t any academic institution nor, for that matter, any pharmaceutical company that can compare with the number of drugs that we have put into the cancer clinic in the last five years.”

The latest candidate is an anti-tumor agent known as XK469, an organic chemical that goes by the full name of 2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]propionic acid. “Our laboratory, under the direction of Dr. Thomas Corbett, was screening drugs from the DuPont Company, which regularly sends us part of its inventory to look for anti-cancer agents,” said Dr. Horwitz, who is widely known for his development of the AIDS treatment known as AZT. “We ran them through a very fast screen to determine in vitro activity, and from this emerged XK469, which really piqued our interest because it was a solid-tumor-selective agent.”

He noted that there is a critical need for agents that fight solid tumors, like those associated with breast, colon, lung and pancreatic cancer. “These are the tumors that have not responded well to chemotherapy,” he explained.

The developmental therapeutics group is following up the initial finding by conducting animal studies to verify the drug’s anti-tumor potential. So far, the researchers have found that XK469 reduces the size of solid tumors and increases survival in mice. Dr. Horwitz added, “It’s not unusual to see cures with certain types of tumors.” The group will also be studying the drug’s effect on human tumor tissue that has been transplanted into mice. “This will give us at least some idea about how this drug is going to behave against human tumors.”

Studies are continuing in Dr. Horwitz’s lab through a five-year, $900,000 grant from the National Institutes of Health. The work will include an investigation into the drug’s mechanism of action, which is currently unknown, and additional research to enhance the activity of XK469 against solid tumors. At the same time, investigators at WSU’s School of Medicine in conjunction with DuPont and the National Cancer Institute are gearing up for Phase I clinical trials of XK469. “We’ll be looking at the toxicology of the agent in humans in the Phase I trial,” Dr. Horwitz said.

He concluded, “At this point, we won’t know how XK469 will fare as an anti-tumor drug in humans, but it looks very good at this juncture in our animal studies, particularly in the spectrum of solid tumors that it affects.”