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
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 2,500+ scientific posters on ePosters
  • More Than 3,700+ 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

Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Tuesday, August 04, 2015
Crystal Clear Images Uncover Secrets of Hormone Receptors
NIH researchers gain better understanding of how neuropeptide hormones trigger chemical reactions in cells.
Monday, August 03, 2015
High-Resolution 3D Images Reveal the Muscle Mitochondrial Power Grid
NIH mouse study overturns scientific ideas on energy distribution in muscle.
Friday, July 31, 2015
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Monday, July 27, 2015
Young South African Women can Adhere to Daily PrEP Regimen as HIV Prevention
NIH-funded study finds men in Bangkok, Harlem also successful in taking daily dose.
Saturday, July 25, 2015
Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
Tuesday, July 21, 2015
NIH Joins Public-Private Partnership to Fund Research on Autism Biomarkers
Biomarkers Consortium project to improve tools for measuring and treating social impairment in children with autism.
Tuesday, July 21, 2015
NIH Study Identifies Gene Variant Linked to Compulsive Drinking
Mice carrying the Met68BDNF gene variant would consume excessive amounts of alcohol.
Tuesday, July 21, 2015
HIV Control Through Treatment Durably Prevents Heterosexual Transmission of Virus
NIH-funded trial proves suppressive antiretroviral therapy for HIV-infected people effective in protecting uninfected partners.
Tuesday, July 21, 2015
Early Antiretroviral Therapy Prevents Non-AIDS Outcomes in HIV-infected People
NIH-supported findings illustrate manifold benefit of therapy.
Tuesday, July 21, 2015
Futuristic Brain Probe Allows for Wireless Control of Neurons
NIH-funded scientists developed an ultra-thin, minimally invasive device for controlling brain cells with drugs and light.
Saturday, July 18, 2015
House Votes in Favor of Bill Boosting NIH Funding
The US House of Representatives today overwhelmingly voted in favor of a bill that would increase funding to the NIH by about $10 billion, help speed the development of new drugs, and advance precision medicine initiatives.
Monday, July 13, 2015
NIH-funded Vaccine for West Nile Virus Enters Human Clinical Trials
Enrollment is expected to be completed by December 2015.
Tuesday, July 07, 2015
In Blinding Eye Disease, Trash-Collecting Cells Go Awry, Accelerate Damage
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Friday, July 03, 2015
Boys More Likely to Have Antipsychotics Prescribed, Regardless of Age
NIH-funded study is the first look at antipsychotic prescriptions patterns in the U.S.
Thursday, July 02, 2015
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Lab-on-a-Chip Offers Promise for TB and Asthma Patients
A device to mix liquids using ultrasonics is the first and most difficult component in a miniaturized system for low-cost analysis of sputum from patients with pulmonary diseases such as tuberculosis and asthma.
Intracellular Microlasers Could Allow Precise Labeling of up to a Trillion Individual Cells
MGH investigators have induced structures incorporated within individual cells to produce laser light at wavelengths that differ based on the size, shape and composition of each microlaser, allowing precise labeling of individual cells.
Real-Time Imaging of Lung Lesions During Surgery
Targeted molecular agents cause lung adenocarcinomas to fluoresce during surgery, according to pilot report.
Watching a Tumour Grow in Real-Time
Researchers from the University of Freiburg have gained new insight into the phases of breast cancer growth.
Protein Related to Long Term Traumatic Brain Injury Complications Discovered
NIH-study shows protein found at higher levels in military members who have suffered multiple TBIs.
Childhood Cancer Cells Drain Immune System’s Batteries
Cancer cells in neuroblastoma contain a molecule that breaks down a key energy source for the body’s immune cells, leaving them too physically drained to fight the disease.
Urine Proteins Point to Early-Stage Pancreatic Cancer
A combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, researchers at the BCI have shown.
Researcher Discovers Trigger of Deadly Melanoma
New research sheds light on the precise trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, pinpointing the precise place in the process where "traveling" cancer turns lethal.
New Vaccine For Chlamydia to Use Synthetic Biology
Prokarium Ltd, a biotechnology company developing transformational oral vaccines, have announced new funding from SynbiCITE, the UK’s Innovation and Knowledge Centre for Synthetic Biology.
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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!