Navigation Links
TGen finds protein inhibitor revives chemotherapy for ovarian patients
Date:7/6/2010

PHOENIX, Ariz. July 6, 2010 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."


'/>"/>

Contact: Steve Yozwiak
syozwiak@tgen.org
602-343-8704
The Translational Genomics Research Institute
Source:Eurekalert

Related biology news :

1. Terrorist de-radicalization shows promise, comprehensive study finds
2. Air pollution doesnt increase risk of preeclampsia, early delivery, study finds
3. Study finds that simple 2-question survey can better identify hungry children
4. Messenger RNAs are regulated in far more ways than previously appreciated, CSHL team finds
5. Organic pesticides not always greener choice, study finds
6. NIH-supported study finds novel pathway may open doors for new blood pressure treatments
7. Large majority of Americans still believe in global warming, Stanford poll finds
8. Study finds epigenetic similarities between Wilms tumor cells and normal kidney stem cells
9. UM School of Medicine study finds vaginal microbes vary among healthy women
10. Neural tissue contains imbalanced levels of proteins, U-M study finds
11. Jumping genes provide extensive raw material for evolution, Penn study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/22/2016)... , June 22, 2016   Acuant ... and verification solutions, has partnered with RightCrowd ... solutions for Visitor Management, Self-Service Kiosks and ... products that add functional enhancements to existing ... corporations and venues with an automated ID ...
(Date:6/21/2016)... British Columbia , June 21, 2016 /PRNewswire/ ... appointed to the new role of principal product ... been named the director of customer development. Both ... NuData,s chief technical officer. The moves reflect NuData,s ... teams in response to high customer demand and ...
(Date:6/16/2016)... , June 16, 2016 ... size is expected to reach USD 1.83 billion ... Grand View Research, Inc. Technological proliferation and increasing ... applications are expected to drive the market growth. ... , The development of advanced multimodal ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... SAN DIEGO , June 24, 2016 /PRNewswire/ ... that more sensitively detects cancers susceptible to PARP ... individual circulating tumor cells (CTCs). The new test ... of HRD-targeted therapeutics in multiple cancer types. ... therapies targeting DNA damage response pathways, including PARP, ...
(Date:6/23/2016)... ... June 23, 2016 , ... Mosio, a leader ... “Clinical Trials Patient Recruitment and Retention Tips.” Partnering with experienced clinical research professionals, ... providing practical tips, tools, and strategies for clinical researchers. , “The landscape of ...
(Date:6/23/2016)... , June 23, 2016 /PRNewswire/ - FACIT has ... Ontario biotechnology company, Propellon Therapeutics Inc. ... and commercialization of a portfolio of first-in-class WDR5 ... targets such as WDR5 represent an exciting class ... in precision medicine for cancer patients. Substantial advances ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... (Yeast and Mold) microbial test has received AOAC Research Institute approval 061601. , ... tests introduced last year,” stated Bob Salter, Vice President of Regulatory and Industrial ...
Breaking Biology Technology: