‘Repurposed’ drugs may treat rare, resistant cancer

Drug repurposing "is an increasingly promising way to speed up the development of treatments for cancers that do not respond well to standard therapies," says Anette Duensing. (Credit: Sparky/Flickr)

Several drugs already approved  by the FDA, but not previously considered as treatments for a rare type of cancer, may have potential if the cancer becomes resistant to standard  treatment.

The discovery demonstrates that high-throughput screening of already FDA-approved drugs can identify new therapies that could be rapidly moved to the clinic, researchers say.


“This is known as “drug repurposing,” and it is an increasingly promising way to speed up the development of treatments for cancers that do not respond well to standard therapies,” says senior author Anette Duensing, assistant professor of pathology at the University of Pittsburgh Cancer Institute.

“Drug repurposing builds upon previous research and development efforts, and detailed information about the drug formulation and safety is usually available, meaning that it can be ready for clinical trials much faster than a brand-new drug.”

For a new study published in the journal Cancer Research, Duensing and colleagues ran the screening on 89 drugs previously approved by the FDA in an attempt to find more treatment options for patients with gastrointestinal stromal tumors (GISTs), which are uncommon tumors that begin in the walls of the gastrointestinal tract.

About 5,000 cases of GISTs occur each year in the United States with an estimated five-year survival rate of 45 percent in patients with advanced disease, according to the American Cancer Society.

37 compounds

GISTs are caused by a single gene mutation and can be successfully treated with the targeted therapy drug imatinib, known by the trade name Gleevec. However, about half of the patients treated with Gleevec become resistant to the drug within the first two years of treatment.

After studying how samples of GIST responded to various concentrations of the 89 drugs in the laboratory, researchers identified 37 compounds that showed some anticancer activity in at least one of the concentrations tested. Importantly, they note that the most promising candidates all belonged to only two major drug classes: inhibitors of gene transcription and so-called topoisomerase II inhibitors.

Based on these findings, they selected the two most promising compounds for further testing—gene transcription inhibitor mithramycin A, which is in clinical trials to treat Ewing sarcoma, and topoisomerase II inhibitor mitoxantrone—which is used in metastatic breast cancer and leukemia.

Both drugs were highly effective in fighting GIST in laboratory tests. Moreover, the mechanism of action of each drug was linked to the specific underlying biology of these tumors.

“These are very encouraging results,” Duensing says. “The next step will be moving our findings to clinical exploration to see if the results we found in the lab hold up in patients.”

Researchers from Catholic University in Belgium, the University of Heidelberg in Germany, and Kochi Medical School in Japan contributed to the study, which was supported by the American Cancer Society and the Howard Hughes Medical Institute.

Source: University of Pittsburgh