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!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Materials Sciences