Researchers at the University of Pittsburgh Cancer Institute(UPCI) have shown that old drugs may be able to do new tricks in the fighter against cancer.
By screening a library of anticancer drugs approved by the U.S. Food and Drug Administration(FDA) that previously wouldn’t have been considered as a treatment for a rare type of cancer, scientists at the University of Pittsburgh Cancer Institute were surprised when they discovered several potential possibilities to try if the cancer becomes resistant to standard drug treatment.
…’Drug repurposing,’ is an increasingly promising way to speed up the development of treatments for cancers that do not respond well to standard therapies…
The discovery, which was published in the February 15, 2014 issue of Cancer Research, demonstrates that high-throughput screening of drugs already approved by the FDA can identify new 
therapies that could be rapidly moved to the clinic. “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,” said senior author Anette Duensing, M.D., assistant professor of pathology at UPCI. “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.”
Advanced disease
Duensing and her team 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. According to the American Cancer Society (ACS), about 5,000 cases of GISTs occur each year in the United States with an estimated five-year survival rate of 45% in patients with advanced disease.
GISTs are caused by a single gene mutation and can be successfully treated with the targeted therapy drug imatinib mesylate (Gleevec?; Novartis). However, about half of the patients treated with imatinib 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, Duensing and her colleagues identified 37 compounds that showed some anticancer activity in at least one of the concentrations tested. Importantly, they noted 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, the research team selected the two most promising compounds for further testing ? gene transcription inhibitor mithramycin A (Mithracin?)*, 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 noted. “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.”
*This drug is discontinued in the United States.
For more information:
Boichuk S, Lee DJ, Mehalek KR, Makielski KR, Wozniak A, Seneviratne DS, Korzeniewski N, et al. Unbiased compound screening identifies unexpected drug sensitivities and novel treatment options for gastrointestinal stromal tumors. Cancer Res. 2014 Feb 15;74(4):1200-13. doi: 10.1158/0008-5472.CAN-13-1955. Epub 2014 Jan 2.[Article][PubMed]
Illustration: University of Pittsburgh Cancer Institute researchers screened 89 approved cancer drugs to see if any of them would be effective against a rare type of tumor. Surprisingly, 37 of the drugs, or 41.5%, exhibited promising activity against the tumor in laboratory tests, with two identified as candidates for future clinical trials. The brighter colors indicate anti-cancer activity. Illustration Courtesy: UPCI.
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