Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Measuring enzymes at end of cancer pathway predicts outcome of Tarceva, Taxol

18.04.2005


Researchers at The University of Texas M. D. Anderson Cancer Center have developed a way to test whether the new targeted therapy Tarceva and the widely used chemotherapy drug Taxol are effectively killing tumor cells. They say that with further refinement, the test may make it possible to accurately assess whether patients are responding to these agents, as well as potentially others, within days of beginning therapy.



In two different studies being presented at the annual meeting of the American Association for Cancer Research (AACR), the research team will describe how the test measures the activity of several members of the cyclin-dependent kinase (CDK) family of enzymes, which are the triggering molecules that allow a cell to grow and divide. CDK cell cycle enzymes are the end target of numerous cellular pathways that are involved in cancer development and progression, the researchers say. Before these studies, no one has been able to accurately test the function of enzymes from a tumor sample, says Naoto Ueno, M.D., Ph.D., an associate professor in the Breast Cancer Translational Research Laboratory and the Department of Blood and Marrow Transplantation. "Testing CDK only has been possible by measuring gene expression, but our industry collaborator has provided a way that lets us test real enzyme activity within a human tumor sample," he says. "Our hope is to be able to use this system as a molecular marker to assess whether an anti-cancer therapy is working."

ABSTRACT # 1670


Sensitivity to Tarceva Depends on CDK2

In the first study, M. D. Anderson researchers found that loss of the CDK2 enzyme strongly correlated with a cancer’s sensitivity to Tarceva.

That means testing activity of CDK2, the enzyme that drives cell division, can reveal whether or not a tumor will respond to Tarceva, says Naoto Ueno, M.D., Ph.D., an associate professor in the Breast Cancer Translational Research Laboratory and the Department of Blood and Marrow Transplantation. If results of this study are verified and validated, "a CDK2 test would provide the best marker yet for effective use of Tarceva," he says. The only experimental predictive test currently available is whether lung cancer cells have a mutation in their epidermal growth factor receptor (EGFR), but that does not predict response to the targeted therapy in other forms of cancer, Ueno says.

"We find here that as long as CDK2 is suppressed, the drug works, so developing an accurate test for CDK2 activity would be a boon for delivering individualized therapy to patients," he says. Such a test, however, will require that patients be given the drug for a short period of time so that the agent’s effect on CDK2 activity can be assessed.

In this study, the researchers exposed 10 different human breast cancer cell lines to varied doses of Tarceva and then measured activity of the CDK enzymes. They found that tumor cell death was significantly dependent on whether CDK2 activity was repressed. They then double checked those findings by "putting CDK2 back," Ueno says. "We found that the effects of Tarceva were reduced when CDK2 was given back to the cells, so this shows us that CDK2 is the real target of Tarceva.

"This presents a concept that describes how Tarceva works, and it also shows that we have a technology that can rapidly measure the true activity of CDK2 in a tumor sample," Ueno says. First author Fumiyuki Yamasaki, M.D., Ph.D., a post-doctoral fellow, is presenting the findings at AACR.

ABSTRACT # 459

Profile CDK to Predict Effectiveness of Taxol

A different research team, headed by Naoto Ueno, M.D., Ph.D., an associate professor in the Breast Cancer Translational Research Laboratory and the Department of Blood and Marrow Transplantation, found in a second study presented at AACR that if activity of several CDK molecules is increased - not decreased as in the Tarceva finding - then the chemotherapy drug Taxol appears to effectively kill breast cancer cells.

Taxol, used to treat a wide spectrum of cancers, works by interrupting the reorganization of the cell that is necessary if it is to divide. While it was known that the primary effect of the drug is to interfere with assembly of the spindle that pulls nuclear chromosomes apart during cell division, Ueno and his colleagues have recently reported that increased activity of CDK1 correlated with a cell’s sensitivity to Taxol.

The CDK enzyme plays a role in cell division, and researchers believe that it functions in part as a monitor of cell cycle activity. Ueno theorizes that if something goes wrong during division - such as if Taxol is interrupting spindle assembly - CDK will become more active in an attempt to correct the problem.

Working with the Sysmex Corporation of Kobe, Japan, the researchers devised a test to measure CDK activity and the expression, simultaneously.

They found that monitoring of two isotypes of CDK activity accurately predicted which tumors would respond to Taxol in the experiments with human breast cancer cell lines and tumor tissues of human xenograft model.

"This provides solid preclinical evidence that we can use toward development of a novel device that can measure CDK activity in human tissue within several hours," Ueno says. He adds that a clinical trial is currently under way that tests CDK activity both before and after patients with breast cancer are treated with Taxol.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>