Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

TGen finds protein inhibitor revives chemotherapy for ovarian patients

06.07.2010
Discovery provides new hope to cancer patients with few treatment options

Investigators at the Translational Genomics Research Institute (TGen) have discovered a way that may help ovarian cancer patients who no longer respond to conventional chemotherapy.

A scientific paper that will be published in the September issue of the journal Gynecologic Oncology describes how the inhibition of a protein, CHEK1, may be an effective element to incorporate into therapies for women with ovarian cancer.

The research led by TGen's Dr. David Azorsa, a Senior Investigator, and Dr. Shilpi Arora, a Staff Scientist, found that inhibiting CHEK1 by a small molecule known as PD 407824, enabled ovarian cancer cells to be attacked again by cisplatin, a widely used platinum-based chemotherapy drug for women with ovarian cancer.

"PD 407824 is only available for laboratory research, but other drugs inhibiting CHEK1 are already used to treat patients in the clinic," said Dr. Raoul Tibes, one of the paper's senior a co-authors and an Associate Investigator in TGen's Clinical Translational Research Division.

The prognosis remains poor for patients with ovarian cancer, which kills nearly 14,600 women in the U.S. annually. The standard treatment for cancer of the ovaries, which produce human egg cells, is surgical removal of the cancer, followed by chemotherapy.

The TGen team proved their method in the research laboratory, which is very encouraging, considering that the use of protein inhibitors in combination with cisplatin, is also proving to be effective in clinical trials with cancer patients.

"The clinical relevance is high, as such novel molecular concepts — inhibiting the repair of cancer cells after treatment with chemotherapies — are in development for many different cancers," said Dr. Tibes, a medical oncologist who treats patients with advanced cancers at TGen Clinical Research Services (TCRS) at Scottsdale Healthcare.

"We actually have similar drug combinations that go after preventing cancer cells to repair themselves, in the clinic already, and we have seen early exciting results. Patients whose tumors had stopped responding to conventional chemotherapy have been made sensitive again, meaning some of these patients responded again to the chemotherapy. The importance of the paper is that it provides evidence that combinations of cisplatin and CHEK1 inhibitors may be worthwhile pursuing in patients with ovarian cancer," said Dr. Tibes.

TCRS is a partnership between TGen and Scottsdale Healthcare that enables laboratory discoveries to be quickly translated into effective therapies for patients at the Virginia G. Piper Cancer Center at Scottsdale Healthcare.

For this research, TGen investigators used cutting-edge technology to screen 572 kinases, the body's protein enzymes that affect how cells function. They discovered 55 siRNAs — strands of RNA molecules that affect the expression of genes — that to some degree enabled cisplatin to slow the growth of cancer cells.

According to the paper, one of those small molecule inhibitors, PD 407824, was especially effective in sensitizing ovarian cancer cells, SKOV3 and OVCAR3, to the growth inhibiting effects of cisplatin. PD 407824 and SB 218078 were the two small molecule inhibitors to CHEK1, that were found to sensitize pancreatic cancer cells to the chemotherapy drug gemcitabine, according to a paper published by the same group last year in the Journal of Translational Medicine.

"Our new data provide kinase targets that could be exploited to design better therapeutics for ovarian cancer patients," said Dr. David Azorsa, Head of TGen's Biological Therapeutics Lab and the senior author of the paper published in Gynecologic Oncology.

In addition, Shilpi Arora, a TGen Staff Scientist and the paper's lead author, said this data, "also demonstrate the effectiveness of high-throughput RNAi screening as a tool for identifying sensitizing targets to known and established chemotherapeutic agents."

About TGen

The Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. TGen is affiliated with the Van Andel Research Institute in Grand Rapids, Michigan. For more information, visit: www.tgen.org.

Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

Steve Yozwiak | EurekAlert!
Further information:
http://www.tgen.org

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>