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

Compound Induces Antitumor Protein

Published: Tuesday, March 05, 2013
Last Updated: Tuesday, March 05, 2013
Bookmark and Share
The finding may improve on current approaches—now in clinical trials—that target this biological pathway.

Programmed cell death, or apoptosis, is the process by which the body eliminates unwanted cells, such as those damaged beyond repair. Apoptosis also plays a role in cancer, as cells that avoid apoptosis can divide uncontrollably and develop into tumors. Researchers have been searching for ways to selectively boost apoptosis in cancer cells without harming normal cells.

TRAIL (Tumor necrosis factor–related apoptosis-inducing ligand) is a protein the body produces to regulate apoptosis. It can induce apoptosis in a wide range of human cancer cell lines. Ongoing clinical trials are testing modified versions of the protein as well as antibodies that activate its receptor on the surfaces of cancer cells. However, these TRAIL-based therapies face several practical obstacles, including cost.

A research team led Dr. Wafik El-Deiry at the Penn State College of Medicine and Penn State Hershey Cancer Institute set out to try a different approach. They screened a collection of small molecules from NIH’s National Cancer Institute (NCI), looking for molecules capable of up-regulating TRAIL gene expression in human cancer cells. The study, funded in part by NCI, appeared on February 6, 2013, in Science Translational Medicine.

The scientists found a small molecule called TIC10 that increased activity of the TRAIL pathway. The compound induced apoptosis in a broad range of cancer cell lines but not in normal cells. In live mice, TIC10 caused regression of several types of human tumor grafts more effectively than TRAIL itself. The compound also helped prolonged survival in mouse models of cancer. The researchers saw no adverse effects at doses up to 10 times a therapeutic dose.

TIC10 boosted levels of TRAIL throughout the mouse body, including the brain. This suggested that, unlike many chemotherapy agents, TIC10 can cross the intact blood-brain barrier. The compound could induce apoptosis in laboratory cells from glioblastoma multiforme, the most common type of malignant brain tumor in adults. TIC10 also helped double the survival of mice bearing grafts of these human tumors and, when given in combination with the drug bevacizumab (Avastin), tripled survival.

Further experiments revealed the mechanism by which TIC10 exerts its effects. The compound inactivates 2 proteins called Akt and ERK. These regulate another protein called Foxo3a, which in turn regulates TRAIL expression. The net effect of TIC10 is to cause Foxo3a to boost TRAIL production. This information will be important for the clinical translation of TIC10. Other agents targeting these biological pathways can now also be explored.

“I was surprised and impressed that we were able to do this,” El-Deiry says. “Using a small molecule to significantly boost and overcome limitations of the TRAIL pathway appears to be a promising way to address difficult-to-treat cancers using a safe mechanism already used in those with a normal effective immune system. This candidate new drug, a first-in-its-class, shows activity against a broad range of tumor types in mice and appears safe at this stage.”

The team is planning to bring TIC10, also now known as ONC201, into clinical trials.


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 3,000+ scientific posters on ePosters
  • More than 4,400+ 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 TechnologyNetworks.com 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.

Related Content

Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Visualizing a Cancer Drug Target at Atomic Resolution
Using cryo-electron microscopy, researchers were able to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells.
Wednesday, February 10, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Friday, February 05, 2016
Biomarkers Outperform Symptoms in Parsing Psychosis Subgroups
Multiple biological pathways lead to similar symptoms - NIH-funded study.
Thursday, December 10, 2015
NIH Supports New Studies to Find Alzheimer’s Biomarkers in Down Syndrome
Initiative will track dementia onset, progress in Down syndrome volunteers.
Tuesday, December 01, 2015
Dementia Linked to Deficient DNA Repair
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer’s disease.
Tuesday, December 01, 2015
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
NIH Funding Targets Gaps in Biomedical Research
New awards support emerging issues in cutting-edge biomedical research fields.
Tuesday, October 06, 2015
NIH Framework Points The Way Forward For Developing The President’s Precision Medicine Initiative
The NIH Advisory Committee to the Director has presented to NIH Director Francis S. Collins, M.D., Ph.D., a detailed design framework for building a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine.
Monday, September 21, 2015
Beth Israel Cardiology Team Awarded $3 Million by NIH
Work will help predict outcomes in patients with heart disease.
Friday, September 18, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Scientists Uncover Nuclear Process in the Brain that May Affect Disease
NIH-funded study highlights the possible role of glial brain cells in neurological disorders.
Tuesday, August 18, 2015
Scientific News
Potential “Good Fat” Biomarker
New method to measure the activity of energy consuming brown fat cells could ease the testing weight loss drugs.
Computational Model Finds New Protein-Protein Interactions
Researchers at University of Pittsburgh have discovered 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia.
New Insights into Gene Regulation
Researchers have solved the three-dimensional structure of a gene repression complex that is known to play a role in cancer.
Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Soy Shows Promise as Natural Anti-Microbial Agent
Soy isoflavones and peptides may inhibit the growth of microbial pathogens that cause food-borne illnesses, according to a new study from University of Guelph researchers.
Potential Target for Revolutionary Antibiotics
An international team of including the Lomonosov Moscow State University researchers discovered which enzyme enables Escherichia coli bacterium (E. coli) to breathe.
DNA Barcodes Gone Wild
A team of researchers at University of Toronto’s Donnelly Centre and Sinai Health System’s Lunenfeld-Tanenbaum Research Institute (LTRI) has developed a new technology that can stitch together DNA barcodes inside a cell to simultaneously search amongst millions of protein pairs for protein interactions.
Biomarkers for Profiling Prostate Cancer Patients
Exiqon A/S has announced the publication of validation of prognostic microRNA biomarkers for the aggressiveness of prostate cancer in independent cohorts.
Grant to Fund Million Peaks Project
The European Research Council (ERC) has awarded a prestigious Advanced Grant to Prof. Peter Schoenmakers, Prof. Albert Polman and Prof. Huib Bakker, all three of whom work at the University of Amsterdam (UvA).
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Scroll Up
Scroll Down
SELECTBIO

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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!