Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein ‘Switches’ Could Turn Cancer Cells Into Tiny Chemotherapy Factories

27.09.2011
Johns Hopkins researchers have devised a protein “switch” that instructs cancer cells to produce their own anti-cancer medication.

In lab tests, the researchers showed that these switches, working from inside the cells, can activate a powerful cell-killing drug when the device detects a marker linked to cancer. The goal, the scientists said, is to deploy a new type of weapon that causes cancer cells to self-destruct while sparing healthy tissue.

This new cancer-fighting strategy and promising early lab test results were reported this week in the online early edition of Proceedings of the National Academy of Sciences. Although the switches have not yet been tested on human patients, and much more testing must be done, the researchers say they have taken a positive first step toward adding a novel weapon to the difficult task of treating cancer.

One key problem in fighting cancer is that broadly applied chemotherapy usually also harms healthy cells. In the protein switch strategy, however, a doctor would instead administer a “prodrug,” meaning an inactive form of a cancer-fighting drug. Only when a cancer marker is present would the cellular switch turn this harmless prodrug into a potent form of chemotherapy.

“The switch in effect turns the cancer cell into a factory for producing the anti-cancer drug inside the cancer cell,” said Marc Ostermeier, a Johns Hopkins chemical and biomolecular engineering professor in the Whiting School of Engineering, who supervised development of the switch.

“The healthy cells will also receive the prodrug,” he added, “and ideally it will remain in its non-toxic form. Our hope is that this strategy will kill more cancer cells while decreasing the unfortunate side effects on healthy cells.”

To demonstrate that these switches can work, the research team successfully tested them on human colon cancer and breast cancer cells in Ostermeier’s lab and in the laboratory of James R. Eshleman, a professor of pathology and oncology in the Johns Hopkins School of Medicine.

“This is a radically different tool to attack cancers,” said Eshleman, a co-author of the PNAS journal article, “but many experiments need to be done before we will be able to use it in patients.”

The next step is animal testing, expected to begin within a year, Ostermeier said.

Ostermeier’s team made the cancer-fighting switch by fusing together two different proteins. One protein detects a marker that cancer cells produce. The other protein, from yeast, can turn an inactive prodrug into a cancer-cell killer. “When the first part of the switch detects cancer, it tells its partner to activate the chemotherapy drug, destroying the cell,” Ostermeier said.

In order for this switch to work, it must first get inside the cancer cells. Ostermeier said this can be done through a technique in which the switch gene is delivered inside the cell. The switch gene serves as the blueprint from which the cell’s own machinery constructs the protein switch. Another approach, he said, would be to develop methods to deliver the switch protein itself to cells.

Once the switches are in place, the patient would receive the inactive chemotherapy drug, which would turn into a cancer attacker inside the cells where the switch has been flipped on.

Although many researchers are developing methods to deliver anti-cancer drugs specifically to cancer cells, Ostermeier said the protein switch tactic skirts difficulties encountered in those methods.

“The protein switch concept changes the game by providing a mechanism to target production of the anti-cancer drugs inside cancer cells instead of targeting delivery of the anti-cancer drug to cancer cells,” he said.

The lead author of the PNAS study was Chapman M. Wright, who worked on the project as an assistant research scientist in Ostermeier’s lab and who now works for a private biotech company. Co-authors on the paper were Ostermeier, Eshleman and R. Clay Wright (not related to Chapman Wright), a doctoral student in Ostermeier’s lab. Through the Johns Hopkins Technology Transfer office, Ostermeier and Chapman Wright have filed for patent protection covering the protein switch for cancer technology.

The research was funded by the National Institutes of Health. The paper, “A protein therapeutic modality founded on molecular recognition,” can be viewed online at:

http://www.pnas.org/content/early/2011/09/12/1102803108.full.pdf+html

Related links:
Marc Ostermeier’s Lab Page: http://www.jhu.edu/chembe/ostermeier/
Department of Chemical and Biomolecular Engineering:
http://www.jhu.edu/chembe/

Phil Sneiderman | Newswise Science News
Further information:
http://www.jhu.edu

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>