Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Laboratory detective work points to potential therapy for rare, drug-resistant cancer

13.02.2014
University of Pittsburgh Cancer Institute (UPCI) scientists have shown that old drugs might be able to do new tricks.

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.

Credit: UPCI

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.

About UPCI

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.

http://www.upmc.com/media

Contact:

Allison Hydzik
Phone: 412-647-9975
E-mail: HydzikAM@upmc.edu
Contact:
Jennifer Yates
Phone: 412-647-9966
E-mail: YatesJC@upmc.edu

Allison Hydzik | EurekAlert!
Further information:
http://www.upmc.edu

More articles from Life Sciences:

nachricht New findings on how cardiac arrhythmias develop
05.05.2015 | CECAD - Cluster of Excellence at the University of Cologne

nachricht Puget Sound's clingfish could inspire better medical devices, whale tags
05.05.2015 | University of Washington

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The random raman laser: A new light source for the microcosmos

Texas A&M University researchers demonstrate how a narrow-band strobe light source for speckle-free imaging has the potential to reveal microscopic forms of life

In modern microscope imaging techniques, lasers are used as light sources because they can deliver fast pulsed and extremely high-intensity radiation to a...

Im Focus: Pulsar with widest orbit ever detected

Discovered by high school research team

A team of highly determined high school students discovered a never-before-seen pulsar by painstakingly analyzing data from the National Science Foundation's...

Im Focus: Erosion, landslides and monsoon across the Himalaya

Scientists from Nepal, Switzerland and Germany was now able to show how erosion processes caused by the monsoon are mirrored in the sediment load of a river crossing the Himalaya.

In these days, it was again tragically demonstrated that the Himalayas are one of the most active geodynamic regions of the world. Landslides belong to the...

Im Focus: Through the galaxy by taxi - The Dream Chaser Space Utility Vehicle

A world-class prime systems integrator and electronic systems provider known for its rapid, innovative, and agile technology solutions, Sierra Nevada Corporation (SNC) is currently developing a new space transportation system called the Dream Chaser.

The ultimate aim is to construct a multi-mission-capable space utility vehicle, while accelerating the overall development process for this critical capability...

Im Focus: High-tech textiles – more than just clothes

Today, textiles are used for more than just clothes or bags – they are high tech materials for high-tech applications. High-tech textiles must fulfill a number of functions and meet many requirements. That is why the Fraunhofer Institute for Silicate Research ISC dedicated some major developing work to this most intriguing research area. The result can now be seen at Techtextil trade show in Frankfurt from 4 to 7 May. On display will be novel textile-integrated sensors, a unique multifunctional coating system for textiles and fibers, and textile processing of glass, carbon, and ceramics fibers to fiber preforms.

Thin materials and new kinds of sensors now make it possible to integrate silicone elastomer sensors in textiles. They are suitable for applications in medical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Green Summit 2015: the summit of the essential

05.05.2015 | Event News

HHL Energy Conference on May 11/12, 2015: Students Discuss about Decentralized Energy

23.04.2015 | Event News

“Developing our cities, preserving our planet”: Nobel Laureates gather for the first time in Asia

23.04.2015 | Event News

 
Latest News

From brittle to plastic in 1 breath

05.05.2015 | Materials Sciences

Ocean currents disturb methane-eating bacteria

05.05.2015 | Earth Sciences

Slowdown after Ice Age sounds a warning for Great Barrier Reef's future

05.05.2015 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>