Corporate Banner
Satellite Banner
Pharma Outsourcing
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
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
Promising Experimental Dengue Vaccine
A clinical trial in which volunteers were infected with dengue virus six months after receiving either an experimental dengue vaccine or a placebo injection yielded starkly contrasting results.
Thursday, March 17, 2016
Eylea Outperforms Avastin for Diabetic Macular Edema with Moderate or Worse Vision Loss
NIH-funded clinical trial shows Eylea, Avastin, and Lucentis perform similarly when vision loss is mild.
Wednesday, March 02, 2016
Vaginal Ring Provides Partial Protection From HIV In Large Multinational Trial
Study finds protective effect is strongest in women over age 25.
Friday, February 26, 2016
Experimental Ebola Antibody Protects Monkeys
Antibody isolated from Ebola survivor can advance to clinical trials.
Friday, February 26, 2016
Experimental Combination Surprises with Anti-HIV Effectiveness
A compound developed to protect the nervous system from HIV surprised researchers by augmenting the effectiveness of an investigational antiretroviral drug beyond anything expected.
Monday, January 25, 2016
Dengue Vaccine Enters Phase 3 Trial
Investigational vaccine to prevent ‘breakbone fever’ developed at NIH.
Friday, January 15, 2016
Trying to Conceive Soon After a Pregnancy Loss May Increase Chances of Live Birth
NIH study finds no reason for delaying pregnancy attempts after a loss without complications.
Wednesday, January 13, 2016
NIH-funded Memory Drug Moves into Phase 1 Clinical Study
Collaboration between NIH and Tetra Discovery Partners leads to development of treatment that may affect cognition.
Monday, January 04, 2016
NIH Unveils FY2016–2020 Strategic Plan
Detailed plan sets course for advancing scientific discoveries and human health.
Thursday, December 17, 2015
Lucentis Effective for Proliferative Diabetic Retinopathy
NIH-funded clinical trial marks first major advance in therapy in 40 years.
Tuesday, November 24, 2015
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Tuesday, October 20, 2015
Scientists Test New Gene Therapy for Vision Loss from a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
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
Scientific News
New Database for Sharing MS Clinical Trial Data
A new database containing nearly 2500 patient records from the placebo arms of nine multiple sclerosis (MS) clinical trials is now available for research by qualified investigators.
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.
BMS’s Opdivo Clinical Trial Shows Promise
Safety profile of the combination regimen from CheckMate -069 was consistent with previously reported studies and adverse events were managed using established safety algorithms.
Treatment of Common Prostate Cancer
Researchers at UTSW have found that the prostate cancer treatments suppress immune response and may promote relapse.
Cancer Drug Could Treat Blood Vessel Deformities
A drug currently being trialled in cancer patients could also be used to treat an often incurable condition that can cause painful blood vessel overgrowths inside the skin.
Structure of Crucial Enzyme Identified
Researchers at UTSW have determined the atomic structure of an enzyme that plays an essential role in cell division and better treatment of cancer.
New Immunotherapy Trial for Type 1 Diabetes
The search for a treatment for Type 1 diabetes (T1D) - which affects over 400,000 people in the UK – will be stepped up with the start of a new phase one clinical trial at Guy’s Hospital in London.
Recruitment of First Patient in Clinical Study
Company has announced recruitment of first patient in clinical study assessing Visco-ease with Beatson Cancer Centre for the treatment of RIX.
Fighting Prostate Cancer
Identifying the most promising compounds which can be used as medications for prostate cancer.
Chi-Med Initiates Sulfatinib Phase III Registration Study
Company has initiated SANET-p, a Phase III registration trial of sulfatinib with pancreatic neuroendocrine tumors (“NETs”).
Scroll Up
Scroll Down
SELECTBIO

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
3,000+ 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!