Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New radiation-free targeted therapy detects and eliminates breast cancer tumors in mice

01.04.2009
Caltech researcher helps develop technique that homes in on aggressive, difficult-to-treat HER2+ breast cancer cells

Combining a compound known as a gallium corrole with a protein carrier results in a targeted cancer therapy that is able to detect and eliminate tumors in mice with seemingly fewer side effects than other breast-cancer treatments, says a team of researchers from the California Institute of Technology (Caltech), the Israel Institute of Technology (Technion) and the Cedars-Sinai Medical Center.

A paper describing their work is highlighted in this week's issue of the online edition of the Proceedings of the National Academy of Sciences (PNAS).

Corroles have very similar structures to the porphyrin molecules used in a well-studied cancer treatment known as photodynamic therapy, or PDT, in which porphyrin compounds injected into the body are exposed to specific wavelengths of laser light. The light prompts the porphyrins to produce active, tumor-killing oxygen radicals.

The difference between porphyrins and corroles, says Harry Gray, Caltech's Arnold O. Beckman Professor of Chemistry and founding director of the Beckman Institute, is that some corroles don't require a laser boost to turn lethal. "The striking thing about gallium corroles is that they apparently kill cancer cells in the dark," says Gray. "We don't yet know exactly how this works, but what we've seen so far tells us that it does work."

He notes that "ongoing work in our laboratories focuses on testing our leading hypotheses for elucidating the mechanism of action."

In the experiments described in the PNAS paper, the team paired a gallium corrole with a carrier protein, then aimed it at cells that carry the human epidermal growth factor receptor 2 (HER2). The presence of a HER2 receptor is the hallmark of about 25 percent of breast cancers, and marks those tumors as particularly aggressive and difficult to treat.

In trials in mice, the targeted corrole was able to shrink tumors at doses five times lower than that of the standard chemotherapeutic agent for HER2-positive tumors, a drug called doxorubicin. In contrast with doxorubicin, the corrole was injected into the bloodstream, rather than directly into the tumor.

"We looked at three groups of mice with human tumors," explains paper coauthor Lali Medina-Kauwe, an assistant professor of medicine at the David Geffen School of Medicine at UCLA, and a faculty research scientist in the Department of Biomedical Science at Cedars-Sinai Medical Center in Los Angeles. "In one, we introduced just the protein carrier, without the corrole; tumor growth in those mice did not change. In other mice, we gave the corrole without the carrier protein; this led to some tumor suppression. But it was the last group, the ones that got the corrole with the carrier protein, that experienced the most therapeutic effect."

"The fact that we can target this compound means we can give it at very low concentrations," adds coauthor Daniel Farkas, director of Cedar-Sinai's Minimally Invasive Surgical Technologies Institute. "Using lower concentrations means less toxicity. Doxorubicin tends to have significant heart toxicity; this therapy seems likely to be much less damaging to the heart."

In addition, adds Medina-Kauwe, targeted compounds can seek out tumors wherever they may be. "One of the beauties of targeting," she says, " is that we can go after metastatic tumors that are too small to be seen."

These targeted gallium corroles are not only effective, they're also easy to study, notes Zeev Gross, the Reba May & Robert D. Blum Academic Chair at Technion, the Israeli Institute of Technology, in Haifa, and another of the paper's coauthors. "In most cases, if people want to get a closer look at a drug in vivo, they have to attach a fluorescent probe to it--and that turns it into a different molecule. But in our case, the active molecule we're tracking does the fluorescing. We get to track the original, unmodified molecule and are hence able to follow its distribution among different organs in live animals."

The difficulty in getting to this point, notes Gray, is that corroles have been challenging to synthesize. "Then Zeev came up with a powerful synthetic method to make corroles," he says. "We went from being able to make a couple of milligrams in two years to being able to make two grams in two days. It really puts corroles on the map."

Gray and Gross further add, "It is truly fulfilling to see how the close collaboration between our research groups at Caltech and the Technion, which started 10 years ago with a focus on developing the fundamental science of corroles, led to pharmaceutical utility when we joined forces with Medina-Kauwe and Farkas, who are experts in cellular biology and biomedical imaging technologies."

The work described in the paper, "Tumor detection and elimination by a targeted gallium corrole," was supported by grants from the National Science Foundation, the National Institutes of Health, the U.S. Department of Defense, Susan G. Komen for the Cure, the Donna and Jesse Garber Award, the Gurwin Foundation, the United States-Israel Binational Science Foundation, and by the U.S. Navy Bureau of Medicine and Surgery.

In addition to the researchers mentioned above, the other scientists contributing to this work include senior scientist Atif Mahammed from Technion, and research associates Hasmik Agadjanian and Altan Rentsendorj, postdoc Vinod Valluripalli, and graduate students Jun Ma and Jae Youn Hwang from Cedars-Sinai.

Lori Oliwenstein | EurekAlert!
Further information:
http://www.caltech.edu
http://pr.caltech.edu/media

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>