Using Old Drugs in New Ways
We already reduce, reuse and recycle. But cancer researchers are exploring a fourth R—repurpose—using drugs approved for treating other diseases to reduce cancer risk and improve outcomes.
By Stephen Ornes
Bruce Bloom, a dentist turned lawyer turned social entrepreneur, says he never set out to join a growing research effort aimed at turning old drugs into new treatments for hard-to-treat diseases like cancer, but that’s exactly what happened.
Bloom leads a nonprofit called Cures Within Reach that has been matching funders with medical research projects for more than 15 years. In 2009, he and his colleagues undertook a routine analysis of their work to find out which of their funded research projects already had started helping patients.
They were surprised to find that the "scientifically interesting" projects—those aimed at creating something new—had yet to show any benefit in treating diseases. They were also stunned to realize that many projects based on "repurposing"—converting existing treatments to new uses, including treating cancer—"were being used clinically to help patients," Bloom says.
"Repurposing" has become a buzzword in recent years, in part because it can be a less expensive and faster approach to get drugs to patients, when compared with developing new drugs from scratch. By using drugs that have already been developed
and tested for safety, researchers can bypass years
of costly work. Biologists, chemists, epidemiologists
and oncologists are working to identify existing compounds created to treat other conditions that have the most potential for cancer prevention or treatment. Though these efforts may not yield a cure for cancer hiding in plain sight, they may generate ways to lower the cost of treatment or increase the effectiveness of cancer drugs. And in a climate of escalating costs for new drugs, finding smart ways to use what is already available appeals to researchers, clinicians and patients alike.
Across all areas of medicine, more than 2,000 unique chemical compounds have been approved for use as drugs by the U.S. Food and Drug Administration (FDA). "Actually, there are a lot more drugs than that, but all the others are essentially copycats of those 2,000," says medical oncologist Jenny Chang of the Methodist Cancer Center in Houston.
The time and effort required to take a new drug from the lab to the clinic are staggering. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), most drugs require between three and six years of development after discovery in the lab before they are ready to be tested for efficacy and safety. Only one in 50 drugs that start with animal and lab testing are ever deemed safe and effective enough to be tested on people. And of all the drugs that enter phase I
clinical trials with human participants—designed to determine a safe dosage and measure side effects—most of those drugs never make it to phase III clinical trials where they are studied for their effectivenss. Only about one in 20 drugs in phase I trials eventually get FDA approval. Pharmaceutical companies spend billions of dollars to shepherd a drug from development through the approval process.
Most drugs were designed with a single purpose in mind—aspirin for pain relief, for example, or metformin to treat type II diabetes. Others were found not to work for their intended purposes and ended up languishing in the vaults of pharmaceutical companies. Repurposing is an opportunity to give these compounds a new life.
Chang offers a hypothetical example: A drug created for a certain condition—say, gout or heart failure—undergoes millions of dollars of development, testing in animal studies, and phase I and II human studies, but fails in a phase III study. That could be the end of the drug. But if geneticists analyze the drug's makeup and find that it has a molecular action against a critical pathway in cancer, potentially "you can take a drug to market and save close to 20 or 30 years of work," she says. "That gets the treatment to a patient much faster, and that's all we want."
Repurposing is not a new idea, but its use in cancer research received a boost in 2003, when researchers unraveled the human genome, allowing them to study the genetic structure of tumors and the molecular mechanisms of treatments.
"Now that we've started to understand the human genome, we are able to figure out the pathways that drive cancer," says Chang, "and we're able to match those pathways to those 2,000 drugs." The idea behind research like Chang's is to use computer programs, capable of handling a lot of data, to identify existing safe and effective molecular compounds that can shut off the molecular switches that help cancer grow and spread. These researchers are not inventing new compounds from scratch. Instead, they're engaged in a kind of high-tech recycling.
The field is growing. In a review article published in the September 2013 Trends in Pharmacological Sciences, researchers from the University of Texas M. D. Anderson Cancer Center in Houston and the University of Texas at Austin reported that "drugs originally identified as antitussive, sedative, analgesic, antipyretic, antiarthritic, anesthetic, antidiabetic, muscle relaxant, immunosuppressant, antibiotic, antiepileptic, cardio-protective, antihypertensive, erectile function enhancing, or angina relieving" are finding new life in cancer research.
Bloom notes that one hurdle to overcome in repurposing inexpensive generic drugs—rather than those still under patent—is persuading pharmaceutical companies to finance the clinical trials needed to get the drugs approved for new uses. On the surface, such a move wouldn't seem to reap big profits for drug makers. "Because most of these are generic drugs and no one will make a profit if they actually help, it's hard to find the money to do a double-blind randomized clinical trial," he says.
On the other hand, repurposing research suggests that low-cost generics may improve the efficacy of existing drugs still under patent, Bloom says. If that's the case, the companies could profit from the combination therapy. And patients could benefit, because one potential bonus of repurposing is to make existing therapies more effective, lessening the need for extensive toxic treatments and multiple rounds of costly drugs.
Ultimately, Bloom says, the challenge in cancer treatment is the same as in many areas of health care: improving care while lowering expenses. "Health care costs are becoming such a substantial thing," he says, and "people are looking for ways to reduce the cost without reducing quality of care. I think repurposing drugs can be a part of that."
STEPHEN ORNES is a contributing writer and a reporter-researcher for Cancer Today. He lives in Nashville, Tenn.