Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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 3,200+ scientific posters on ePosters
  • More Than 4,600+ 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

Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Saturday, June 25, 2016
Rates of Nonmedical Prescription Opioid Use Disorder Double in 10 Years
Researchers at NIH have found that the nonmedical use of prescription opioids has more than doubled among adults in the United States from 2001-2002 to 2012-2013.
Thursday, June 23, 2016
Peanut Allergy Prevention Strategy is Nutritionally Safe
Early-life peanut consumption does not affect duration of breastfeeding or children’s growth and nutrition.
Wednesday, June 22, 2016
NIH Launches Large Study of Pregnant Women in Areas Affected by Zika virus
Researchers at NIH and Fiocruz have begun a study to evaluate the magnitude of health risks that Zika virus infection poses to pregnant women and their developing fetuses and infants.
Wednesday, June 22, 2016
New Imaging Method May Predict Risk of Post-Treatment Brain Bleeding After Stroke
Researchers at NIH have developed technique that provides new insight into stroke.
Tuesday, June 21, 2016
Study Reveals Central Role of Endocannabinoids in Habit Formation
The new study findings point to a previously unknown mechanism in the brain that regulates the transition between goal-directed and habitual behaviors.
Tuesday, June 21, 2016
Predicting Effective Drug Combinations For TB
Researchers analyzed gene regulatory networks to explain the effectiveness of an experimental drug combination against drug-resistant tuberculosis bacteria.
Wednesday, June 15, 2016
Genomic Data Commons Launched
Part of the National Cancer Moonshot, the GDC will centralize and standardize accessible data.
Tuesday, June 07, 2016
Prevention May be Essential to Reducing Racial Disparities in Stroke
Researchers at NIH have found study provides clues to differences in stroke deaths between blacks and whites.
Friday, June 03, 2016
NIH Funds Biobank To Support Precision Medicine Initiative Cohort Program
$142 million over five years will be awarded to the Mayo Clinic to establish the world’s largest research-cohort biobank for the PMI Cohort Program
Friday, May 27, 2016
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Friday, May 27, 2016
New NIH-EPA Research Centers to Study Environmental Health Disparities
Scientists will partner with community organizations to study these concerns and develop culturally appropriate ways to reduce exposure to harmful environmental conditions.
Thursday, May 26, 2016
Nanoparticles Target, Transform Fat Tissue
Nanoparticles designed to target white fat and convert it to calorie-burning brown fat slowed weight gain in obese mice without affecting food intake. This proof-of-concept work could lead to new therapies to treat obesity.
Wednesday, May 25, 2016
Visual Impairment, Blindness Cases in U.S. Expected to Double by 2050
Researchers at NIH have suggested that there is a need for increased screening and interventions to identify and address treatable causes of vision loss.
Friday, May 20, 2016
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Starving Stem Cells May Enable Scientists To Build Better Blood Vessels
Researchers from the University of Illinois at Chicago College of Medicine have uncovered how changes in metabolism of human embryonic stem cells help coax them to mature into specific cell types — and may improve their function in engineered organs or tissues.
Scroll Up
Scroll Down
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
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!