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 3,300+ scientific posters on ePosters
  • More than 5,000+ 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

New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
How Parkinson’s Disease Alters Brain Activity Over Time
The NIH study provides a new tool for testing experimental medications aimed at alleviating symptoms and slowing the rate at which the diseases damage the brain.
Tuesday, August 16, 2016
Genetic Cause of Rare Pediatric Neuropathy Identified
NIH mouse study identifies the mechanism responsible for a rare form of pediatric neuropathy.
Thursday, August 04, 2016
Uncovering Rhinovirus C Structure
Researchers have determined the structure of rhinovirus C. Their findings may aid the development of antiviral therapies and vaccines.
Wednesday, July 27, 2016
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Friday, May 27, 2016
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
Scientific News
Signaling Molecule Regulates Release of the Hunger Hormone Ghrelin
Researchers at UT Southwestern have identified that the blocking release of the hormone ghrelin may mediate low blood sugar effect in children taking beta blockers.
Telomere Replenishment in Real Time
Researchers have visualised the process of telomere attachment to chromosomes through single-molecule imaging.
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
World's Most In-Depth Study to Detect Alzheimer's Disease
A multisite team will see the most thorough and vigorous testing for Alzheimer's ever performed on volunteers.
Zika Proteins Responsible for Microcephaly Identified
Researchers have undertaken the first study to examine Zika infection in human neural stem cells from second-trimester fetuses.
Pinpointing Key Influenza-Fighting Immune Trigger
Immunologists have identified the protein trigger that recognises influenza virus infection in cells and triggers their death.
Uncovering Constructor Proteins
Scientists have discovered a new bacterial cell wall builder that could be a target for antibiotic development.
Studying Protein, Synapse Interactions
New research identifies, for the first time, the role of certain proteins in synapse opperation and function.
Biomarker Breakthrough Could Improve Parkinson’s Treatment
A new method of tracking Parkinson's progression could aid evaluation of new and experimental treatments to slow or stop the disease.
PARP Proteins Explore Therapeutic Targets in Cancer
Researchers at UTSW have identified a previously unknown role of a certain class of proteins that opens the door to explore therapeutic targets in cancer and other disease.
Scroll Up
Scroll Down
Skyscraper Banner

SELECTBIO Market Reports
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!