Teaching old drugs new tricks

Developing a new cancer drug in the laboratory, then shepherding it through the steps required to seek Food and Drug Administration approval requires an average of 13 years and $1.8 billion, according to the National Institutes of Health.

Even then, only 5 percent of oncology drugs ultimately are approved for cancer treatment. And many of these are highly expensive and create numerous side effects.

To deliver drugs to patients faster, more efficiently and at less cost, scientists have begun studying whether pharmaceuticals already approved to treat one disease can be safely and effectively used to treat another – a process known as drug repurposing.

“An existing drug has already been through years of preclinical and clinical studies required by the FDA, therefore much of the heavy lifting has already been done,” says Michael Rosenblum, Ph.D., professor of Experimental Therapeutics. “Starting with an old drug with a known clinical history can significantly reduce the time and cost associated with developing new cancer drugs.”

Many unrelated diseases share common molecular characteristics, Rosenblum explains. This means that two completely different diseases may respond to the same drug.

“It’s estimated that about 90 percent of FDA-approved compounds can be used for more than one purpose,” he says. “We can teach old drugs new tricks by matching them to the molecular pathways of other diseases.”

Drugs show accidental success in treating other conditions

Most successful cases of drug repurposing are largely serendipitous discoveries – coming more by chance than intent. Here are a few examples:

• Tamoxifen was originally designed to block estrogen in the hopes of preventing pregnancy. It failed as a contraceptive, but research showed the drug blocks the estrogen which fuels certain types of breast cancer. Today, tamoxifen is widely prescribed to treat and prevent breast cancer.
• Minoxidil was initially used as a high blood pressure medication, but was reformulated into the topical cream Rogaine after patients experienced hair regrowth.
• Viagra was first tested as a cardiovascular disease treatment, but when study participants began experiencing erections, the drug was redesigned as an erectile dysfunction therapy.

Hundreds of repurposing possibilities still exist, Rosenblum says.

“More and more, repurposing is being recognized as a faster, cheaper and safer way to drive therapies to patients,” he says. “It’s the smart way to develop new drugs.”

Repurposed Drugs

Raloxifene
The FDA approved Raloxifene to reduce the risk of invasive breast cancer in postmenopausal women in 2007. It was initially developed to treat osteoporosis.

Thalidomide
This drug started out as a sedative in the late 1950s, and soon doctors began prescribing it to prevent nausea during pregnancy. It caused thousands of severe birth defects, but in 1998 thalidomide found a new use as a treatment for leprosy. In 2006, it was approved for multiple myeloma, a condition in which cancer cells accumulate in the bone marrow.

Tamoxifen
In addition to treating and preventing breast cancer, researchers discovered in 2007 that tamoxifen also helps people with bipolar disorder by blocking the enzyme PKC, which goes into overdrive during the manic phase of the disorder.

Pentostatin
This drug was tested as a chemotherapy for T-cell-related leukemias, but the cancers didn’t respond to the drug. Later, National Cancer Institute researchers found that the drug was successful in treating a rare leukemia that is B-cell related, called Hairy Cell Leukemia.

Celebrex
A popular osteoarthritis drug, Celebrex has also been shown to decrease the risk of additional polyp formation in people who’ve had colon cancer in the past.

Metformin
In the mid-2000s, researchers found that patients taking this common diabetes drug had a significantly lowered risk for breast cancer.

ATRA
All-trans retinoic acid (ATRA) has historically been used to treat severe acne. But researchers found that when ATRA is combined with chemotherapy, the drug combination significantly decreases the chance of relapse among leukemia patients in remission.

Methotrexate
This chemotherapy drug was developed in the 1950s and since then is typically administered at a very high dose to cancer patients. At a low dose, it has become the standard of care for autoimmune diseases such as rheumatoid arthritis or psoriasis.