Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Preclinical Tests Shows Agent Stops “Slippery” Proteins from Binding, Causing Ewing Sarcoma

Published: Friday, May 17, 2013
Last Updated: Friday, May 17, 2013
Bookmark and Share
Some tumors regressed to the point that cancer cells could not be detected microscopically.

Their study, which will be presented at the 2013 annual meeting of the American Society of Clinical Oncology, provides pre-clinical evidence necessary to initiate a clinical trial.

“This agent has the potential to be more effective, and considerably less toxic, than the current drugs now used to treat this rare cancer,” says the study’s lead investigator, Jeffrey Toretsky, MD, a pediatric oncologist and researcher at Georgetown Lombardi, part of Georgetown University Medical Center.

The agent, (S)-YK-4-279, was developed by Toretsky and his colleagues, including scientists in GUMC’s Center for Drug Discovery. Based on early promising studies of the compound, Toretsky established TDP Biotherapeutics, Inc. to manufacture the agent. Toretsky says TDP Biotherapeutics, Inc. is preparing a U.S. Food and Drug Administration (FDA) investigational new drug (IND) application for (S)-YK-4-279 so that a clinical trial can be initiated.

In the United States, about 500 children and young adults are diagnosed with the cancer annually, and they are treated with a combination of five different chemotherapy drugs. Between 60 to 70 percent of patients survive more than five years, but with many late effects from therapy. Few treatments lead to a cure for patients whose cancer progresses, Toretsky says.

Ewing sarcoma is caused by the exchange of DNA between two chromosomes. The resulting EWSR1-FLI1 gene produces a fusion protein, EWS-FLI1, responsible for development of the cancer. In 2006, Toretsky and his team discovered that the fusion protein binds to another protein, RNA helicase A (RHA), which is important for cancer progression.

The (S)-YK-4-279 agent they developed is considered unique because it stops the two proteins — EWS-FLI1 and RHA — from interacting. “Scientists have long thought it impossible to block protein-protein interaction because the surface of these proteins are too slippery and flexible for a drug to bind to,” Toretsky says. “Our agent challenges that conventional thinking.”

To test the agent, the researchers developed a rat model of Ewing sarcoma and figured out how to deliver a continuous drip of the drug to the animals. “We found that cancer cells need a continuous exposure at low concentrations for the drug to be of maximum effectiveness,” Toretsky says. “And this strategy works extremely well in these animal models. The drug appears to be very successful.”

Toretsky is an inventor on a patent application that has been filed by Georgetown University related to the technology described. He has an ownership interest in TDP Biotherapeutics, to which the technology has been licensed for research and development.

The FDA has granted the TDP Biotherapeutics company orphan drug status (Orphan Drug Act), which qualifies the sponsor of a product to receive tax credit and marketing incentives. The study was funded by a grant from the National Cancer Institute (RC4 CA156509) issued under the American Recovery and Reinvestment Act (R01CA138212).

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,100+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Scientific News
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Unravelling the Role of Key Genes and DNA Methylation in Blood Cell Malignancies
Researchers from the University of Nebraska Medical Center have demonstrated the role of Dnmt3a in safeguarding normal haematopoiesis.
Agilent Presents Early Career Professor Award to Dr. Roeland Verhaak
JAX professor recognized for the development and implementation of workflows for the analysis of big-data from transcriptomics to next generation sequencing approaches.
Ovarian Cancer Insight
Study showed tumours release cytokines to attract macrophages, which secrete growth factors that in turn promote tumour growth.
Bacterial Genes Boost Current in Human Cells
Borrowing and tweaking bacterial genes to enhance electrical activity might treat heart, nervous system injury.
Less Frequent Cervical Cancer Screening
HPV-vaccinated women may only need one screening every 5 to 10 years with screening starting later in life.
Questioning the Safety of Selenium to Combat Cancer
Research indicates the need for change in practice as selenium supplements cannot be recommended for preventing colorectal cancer.
Supercomputers Could Improve Cancer Diagnostics
Researchers push the boundaries of cancer research through high-performance computing to map the human immunone.
Transgenomic, Precipio Diagnostics Merger
Merger will creates a robust diagnostic platform focused on improving accuracy of cancer diagnoses.
Leukaemia Cell Movement Gives Clues to Tackling Treatment-Resistant Disease
Researchers at Imperial College London have suggested that the act of moving itself may help the cells to survive, possibly through short-lived interactions with an array of our own cells.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,100+ scientific videos