Navigation Links
Lombardi research teams hone in on treatments for osteosarcoma and Ewing's sarcoma
Date:4/20/2010

Washington, DC Most cancers arise from the epithelium, the tissue that lines the body and the organs, but sarcomas come from connective tissue cells, like the bones. At Georgetown Lombardi Comprehensive Cancer Center, research have engaged in a full-court press to develop new therapies to treat osteosarcoma and Ewing's sarcoma, the two most common bone tumors in children, adolescents and young adults.

At the AACR 101st Annual Meeting 2010, they offer new molecular insights into the translocation that causes Ewing's sarcoma, a genetic exchange between chromosomes that results in a fused gene that produces an oncogenic protein. These findings, coupled with use of sophisticated drug design technology, have led to identification of three new targets for potential treatment of this rare cancer. Additionally, researchers have identified two small molecules that have the potential to prevent or treat spread of osteosarcoma, a very aggressive cancer. (Embargoes listed with each abstract summary that follows).

"Scientific studies in the past decade identified very promising molecular targets that play a major role in tumor progression and invasion. With the help of a multidisciplinary team of scientists at Lombardi, we are now focusing on developing small molecules that can hit these targets," says Aykut ren, M.D., assistant professor in the Department of Oncology at Lombardi. "With this truly translational experimental approach, we may be able to optimize our small molecules for clinical trials in the near future."

ABSTRACT SUMMARIES

Targeting of EWS-FLI1 with small molecule YK-4-279 reduces xenograft growth by disruption of disordered protein-protein interactions (abstract #3411)

EMBARGO: Tuesday, April 20, 2010, 9:00 am ET

Author's summary: "Because the oncoprotein that causes the Ewing's sarcoma is so disordered, we reasoned that it might be possible to use a small molecule to target that protein and disrupt a key protein-protein interaction, leading to decreased cancer growth. Using state-of-the art tools, we screened 3000 compounds and found one, YK-4-279, that significantly inhibited this protein-protein binding. We have now demonstrated that YK-4-279 has a detrimental effect on Ewing's sarcoma both in vitro and in vivo, providing us with an oncogenic target and a lead compound for therapeutic testing." Jeffrey Toretsky

Authors: Jeffrey A. Toretsky, Hayriye V. Erkizan, Yali Kong, Julie S. Barber-Rotenberg, Milton L. Brown, and Aykut ren, of Georgetown Lombardi Comprehensive Cancer Center; Melinda Merchant, of Pediatric Oncology Branch, National Institutes of Health

To be presented: Tuesday, April 20, 9:00 am -12:00 pm; Exhibit Hall A-C, Poster Section 18; Board 12


EWS-FLI1 is regulated by acetylation (Abstract # 3897)

EMBARGO: Tuesday, April 20, 2010; 2:00 pm ET

Author's summary: "EWS-FLI1 is a protein specific to Ewing's Sarcoma Family of Tumors (ESFT). EWS-FLI1 is a transcription factor and thereby a central regulator of ESFT cell survival and tumor growth. The mechanisms controlling its function and stability are not well understood. We show, for the first time, that EWS-FLI1 is modified by acetylation, a process that can in fact regulate both stability and function of proteins. Drugs called Histone Deacetylase Inhibitors (HDI) inhibit the reverse process, the deacetylation of proteins, and are promising in the treatment of a variety of cancers. HDI act mainly (but not solely) by deacetylating histone protein, and are very active in inducing cell death of ESFT cells. We investigate how acetylation regulates EWS-FLI1 and the possibility of EWS-FLI1 being a specific target for the activity of HDI in ESFT cells." Silke Schlottmann

Authors: Silke Schlottmann, Hayriye V. Erkizan, Julie Barber-Rotenberg, Aykut Uren, Maria L. Avantaggiati, and Jeffrey A. Toretsky. Georgetown Lombardi Comp. Cancer Ctr., Washington, DC.

To be presented: Tuesday, April 20, 2:00 5:00 pm; Exhibit Hall A-C, Poster Section 2; Board 5


Arsenic trioxide inhibits Ewing sarcoma growth by blocking Hedgehog/GLI pathway (Abstract # 3409)

EMBARGO: Tuesday, April 20, 2010; 9:00 am ET

Author's summary: "The protein GLI1 is important for the growth of many cancers such as pancreatic and brain tumors. We have previously published that the protein GLI1 is important for the growth of Ewing Sarcoma. We show data that an already FDA approved drug Arsenic Trioxide which is used to treat a specific type of leukemia can inhibit the protein GLI1. Arsenic Trioxide can inhibit the growth of a specific type of pediatric brain cancer called Medulloblastoma as well as Ewing sarcoma in mice. Therefore Arsenic Trioxide can be investigated in clinical trials to treat Ewing Sarcoma as well as other types of cancers that depend on hyperactivity of the protein GLI1." Elspeth M. Beauchamp

Authors: Elspeth M. Beauchamp, Olga Rodriguez, Christopher Albanese, Jeffrey A. Toretsky, and Aykut ren, from. Georgetown Lombardi Comp. Cancer Ctr., Washington, DCBeauchamp

To be presented: Tuesday, April 20, 9:00 am - 12:00 pm ET, Exhibit Hall A-C, Poster Section 18, Board 10


EWS-FLI1 as a molecular target: Small molecule inhibitors for a disordered protein (Abstract #2681)

EMBARGO: Monday, April 19, 2010; 2:00 pm ET

Author's summary: "Ewing's sarcoma family of tumors are characterized by the EWS-FLI1 oncogenic fusion protein. Previous studies show that RNA Helicase A (RHA) binds with EWS-FLI1 to enhances the oncogensis of EWS-FLI1 and the interaction between these two proteins can be disrupted by small molecule inhibitors. To test analogues of the lead small molecule, a biophysical assay is necessary to determine binding. AlphaScreen technology allows for a peptide displacement assay to study binding in a 96 well plate format, requiring minimal reagents and a higher-throughput format. Data from binding studies will help to predict and direct the design of more potent analogues." - Julie S. Barber-Rotenberg

Authors: Julie S. Barber-Rotenberg, Yali Kong, Nilan Schnure, Sivanesan Dakshanamurthy, Milton L. Brown, Hayriye V. Erkizan, Aykut Uren. and Jeffrey A. Toretsky, from Georgetown Lombardi Comprehensive Cancer Center; Peter Frazier, Cornell University

To be presented: Monday, April 19, 2:00 pm 5:00 pm; Exhibit Hall A-C, Poster Section 28; Board 14


Phage display identifies novel toxic binding peptides for the disordered oncoprotein EWS-FLI1 (Abstract #3412)

EMBARGO: Tuesday, April 20, 2010, 9 AM

Author's summary: "The EWS-FLI1 protein results from a tumor-specific chromosomal translocation and is uniquely expressed in Ewing's Sarcoma Family Tumors (ESFT). EWS-FLI1 is a disordered protein and thus presents opportunities for manipulating protein-protein interactions, some of which will be specific anti-tumor targets. By looking at and identifying various peptides and their cognate proteins, we can investigate the function of EWS-FLI1 in order to improve therapies for ESFT patients. The A1 peptide, which we focused on specifically, appears to directly bind to the EWS-FLI1 protein and lead to cell death in cells with the EWS-FLI1 fusion protein." - Lauren M. Jacobwitz

Authors: Lauren M. Jacobwitz, Hayriye V. Erkizan, Aykut ren, and Jeffrey A. Toretsky, Georgetown Lombardi Comprehensive Cancer Center

To be presented: Tuesday, April 20, 9:00 am 12:00 pm ET; Exhibit Hall A-C, Poster Section 18; Board 13


Small molecule inhibitors of ezrin as anti-metastatic agents in osteosarcoma (Abstract #1550)

EMBARGO: Monday, April 19, 2010; 9:00 am ET

Author's summary: "Our study is focused on developing new therapies for osteosarcoma (OS). OS is a very aggressive cancer of the bone. Death from OS is generally results from respiratory failure due to spread of cancer to the lungs. Ezrin is a protein in the cell that contributes to the biology of cancer, especially to its growth and spread to other body parts. Accumulating evidence from experimental animal models and human cases suggest that ezrin is a key factor in spread of OS cells. Here we report the discovery of two lead compounds that directly bind to ezrin protein and inhibit its function in multiple assays. These small molecules have the potential to prevent or treat OS spreading to the lungs and significantly improve survival of OS patients." - Glay Bulut

Authors: Glay Bulut, Kevin Chen, Eric Glasgow, Jeffrey A. Toretsky, and Aykut ren, Georgetown Lombardi Comprehensive Cancer Center; Sung-Hyeok Hong, Chand Khanna, Hyun-Shik Lee, and Ira Daar, National Cancer Institute.

To be presented: Monday, April 19, 2010 9:00 am - 12:00 pm ET; Exhibit Hall A-C, Poster Section 23; Board 3


'/>"/>

Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

Related medicine news :

1. Lombardis Shields leads special journal focused on tobacco research
2. GUMCs Lombardi Hosts Symposium Exploring Future of Cancer Research and Personalized Medicine
3. New research identifies modifiable risk factors for heart disease
4. Nuvo Research announces early redemption of 5% convertible debentures
5. Researcher to track spread of disease, malware and power outages
6. UCSF Researchers Identify Regulator of Human Sperm Cells
7. Octapharma Accepting Applications for Research Grants Through March 31
8. Valentine Tailgate Party for the Girls with Festive Ideas from Beauty Research
9. New Research Shows Genes of Pregnant Women and Their Fetuses Can Increase the Risk of Preterm Labor
10. University of Maryland chemist receives Astellas Award for blindness prevention research
11. Developing a cyberinfrastructure for comparative effectiveness in cancer research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/24/2017)... ... February 24, 2017 , ... Congratulations to Head Over Heels’ ... February 12th. Ms. Esparza qualified into this prestigious status after winning the ... Las Vegas, Nevada. Frida is one of approximately 25 gymnasts in the nation ...
(Date:2/23/2017)... ... 23, 2017 , ... The 89th Academy Awards will be celebrated this weekend, ... Policy Center Bunkum Award. We invite you to enjoy our 11th annual tongue-in-cheek “salute” ... is the Center for American Progress (CAP), for its report, Lessons From State Performance ...
(Date:2/23/2017)... Los Angeles, CA (PRWEB) , ... February 23, 2017 , ... ... the first two episodes of WE TV’s “Mama June: From Not to Hot,” which ... of TV notable, “Mama” June Shannon, known to millions from the 2012 reality television ...
(Date:2/23/2017)... California (PRWEB) , ... February 23, 2017 , ... ... Sports Development will host a diverse symposium on “Doping in Sport: ... Law and Sheppard Mullin Richter & Hampton LLP. The symposium will be held ...
(Date:2/23/2017)... ... February 23, 2017 , ... ... that it will soon begin franchising throughout the U.S. starting this spring. Current ... bring the practice of meditation mainstream. Current Meditation will be the first meditation ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... YORK , Feb. 23, 2017  This report ... Thousand by the following Products: Intermediates, ... in the report include Pharmaceuticals, and Agrochemicals. The report ... Japan , Europe , and ... for the period 2015 through 2022. Also, a six-year ...
(Date:2/24/2017)... Research and Markets has announced the addition of the ... report to their offering. ... The latest research Urinary Incontinence Drugs Price Analysis and ... global Urinary Incontinence market. The research answers the following questions: ... for Urinary Incontinence and their clinical attributes? How are they positioned ...
(Date:2/23/2017)... MINNEAPOLIS , Feb. 23, 2017  Cogentix Medical, ... manufactures and markets innovative proprietary products for the urology ... and fiscal year ended December 31, 2016 before the ... The Company will host a conference call and ... on Thursday, March 9, 2017 at 11:00 a.m. Eastern ...
Breaking Medicine Technology: