By screening a library of FDA-approved anticancer drugs that previously wouldn't have been considered as a treatment for a rare type of cancer, UPCI scientists were surprised when they found several potential possibilities to try if the cancer becomes resistant to standard drug treatment.
University of Pittsburgh Cancer Institute researchers screened 89 FDA-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 percent, 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.
The discovery, which will be published in the February 15th issue of Cancer Research, demonstrates that high-throughput screening of already FDA-approved drugs 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."
Dr. 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, 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.
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, Dr. 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, 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," said Dr. Duensing. "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."
Additional co-authors of this study include Sergei Boichuk, M.D., Ph.D., Derek J. Lee, B.S., Keith R. Mehalek, M.S., Kathleen R. Makielski, M.S., Danushka S. Seneviratne, B.S., Rolando Cuevas, M.S., Joshua A. Parry, B.S., Matthew F. Brown, Ph.D., James P. Zewe, B.S., and Shih-Fan Kuan, M.D., Ph.D., all of Pitt; Agnieszka Wozniak, Ph.D., Patrick Schöffski, M.D., M.P.H., and Maria Debiec-Rychter, M.D., Ph.D., all of the Catholic University in Leuven, Belgium; Nina Korzeniewski, Ph.D., of the University of Heidelberg in Germany; and Takahiro Taguchi, M.D., of Kochi Medical School in Japan.
This research was supported by American Cancer Society grant no. RSG-08-092-01-CCG, The Life Raft Group, GIST Cancer Research Fund and the Howard Hughes Medical Institute.
As the only NCI-designated comprehensive cancer center in western Pennsylvania, UPCI is a recognized leader in providing innovative cancer prevention, detection, diagnosis, and treatment; bio-medical research; compassionate patient care and support; and community-based outreach services. UPCI, a partner with UPMC CancerCenter, investigators are world-renowned for their work in clinical and basic cancer research.
Allison Hydzik | EurekAlert!
27.03.2015 | Oak Ridge National Laboratory
How did the chicken cross the sea?
27.03.2015 | Michigan State University
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences
27.03.2015 | Ecology, The Environment and Conservation