Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug from Mediterranean weed kills tumor cells in mice

10.07.2012
'Molecular grenade' now in clinical trials for advanced cancer

Scientists at the Johns Hopkins Kimmel Cancer Center, working with Danish researchers, have developed a novel anticancer drug designed to travel -- undetected by normal cells -- through the bloodstream until activated by specific cancer proteins. The drug, made from a weedlike plant, has been shown to destroy cancers and their direct blood supplies, acting like a "molecular grenade," and sparing healthy blood vessels and tissues.

In laboratory studies, researchers said they found that a three-day course of the drug, called G202, reduced the size of human prostate tumors grown in mice by an average of 50 percent within 30 days. In a direct comparison, G202 outperformed the chemotherapy drug docetaxel, reducing seven of nine human prostate tumors in mice by more than 50 percent in 21 days. Docetaxel reduced one of eight human prostate tumors in mice by more than 50 percent in the same time period.

In a report June 27 in the journal Science Translational Medicine, the researchers also reported that G202 produced at least 50 percent regression in models of human breast cancer, kidney cancer and bladder cancer.

Based on these results, Johns Hopkins physicians have performed a phase I clinical trial to assess safety of the drug and have thus far treated 29 patients with advanced cancer. In addition to Johns Hopkins, the University of Wisconsin and the University of Texas-San Antonio are participating in the trial. A phase II trial to test the drug in patients with prostate cancer and liver cancer is planned.

The drug G202 is chemically derived from a weed called Thapsia garganica that grows naturally in the Mediterranean region. The plant makes a product, dubbed thapsigargin, that since the time of ancient Greece has been known to be toxic to animals. In Arab caravans, the plant was known as the "death carrot" because it would kill camels if they ate it, the researchers noted.

"Our goal was to try to re-engineer this very toxic natural plant product into a drug we might use to treat human cancer," says lead study author Samuel Denmeade, M.D., professor of oncology, urology, pharmacology and molecular sciences. "We achieved this by creating a format that requires modification by cells to release the active drug."

By disassembling thapsigargin and chemically modifying it, the researchers created a form that Denmeade likens to a hand grenade with an intact pin. The drug can be injected and can travel through the bloodstream until it finds the site of cancer cells and hits a protein called prostate-specific membrane antigen (PSMA). PSMA is released by cells lining tumors of the prostate and other areas, and in effect "pulls the pin" on G202, releasing cell-killing agents into the tumor and the blood vessels that feed it, as well as to other cells in the vicinity. Specifically, G202 blocks the function of a protein called the SERCA pump, a housekeeping protein necessary for cell survival that keeps the level of calcium in the cell at the correct level, the researchers report.

"The exciting thing is that the cancer itself is activating its own demise," says senior study author John Isaacs, Ph.D., professor of oncology, urology, chemical and biomedical engineering at Johns Hopkins.

Because the drug is targeted to the SERCA pump, which all cells need to stay alive, researchers say it will be difficult for tumor cells to become resistant to the drug, because they cannot stop making the protein.

The study's co-authors were Annastasiah M. Mhaka, D. Marc Rosen, W. Nathaniel Brennen, Susan Dalrymple, Bora Gurel, Angelo M. DeMarzo, and Michael Carducci of Johns Hopkins; Ingrid Dach, Claus Olesen, Jesper V. Møller, and Poul Nissen of the Danish National Research Foundation and Aarhus University; and Craig A. Dionne of GenSpera Inc.; and S. Brøgger Christensen of the University of Copenhagen.

The work was supported by the Department of Defense Prostate Cancer Research Program, the Prostate Cancer Foundation and David Koch, the Danish Cancer Society, the Danish Research Council for Strategic Research, the Danish National Research Foundation, the Danish Medical Research Council, the Aarhus University Research Foundation, and the National Institute of Health's National Cancer Institute Specialized Program of Research Excellence (CA058236 and CA006973).

Denmeade and Isaacs are consultants for GenSpera Inc. and have received equity and financial compensation. This relationship has been disclosed and is under the management of the Johns Hopkins University School of Medicine Conflict of Interest Committee.

On the Web:

www.hopkinscancer.org

Science Translational Medicine

Vanessa Wasta | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>