TRAIL is a natural anti-tumor protein that suppresses tumor development during immune surveillance -- the immune system's process of patrolling the body for cancer cells. This process is lost during cancer progression, which leads to uncontrolled growth and spread of tumors.
The ability of TRAIL to initiate cell death selectively in cancer cells has led to ongoing clinical trials with artificially created TRAIL or antibody proteins that mimic its action. Use of the TRAIL protein as a drug has shown that it is safe, but there have been some issues, including stability of the protein, cost of the drug, and the ability of the drug to distribute throughout the body and get into tumors, especially in the brain.
"The TRAIL pathway is a powerful way to suppress tumors but current approaches have limitations that we have been trying to overcome to unleash an effective and selective cancer therapy," said Dr. Wafik El-Deiry, professor of medicine and chief of the hematology/oncology division, Penn State College of Medicine. "The TRAIL biochemical cell death pathway naturally lends itself as a drug target to restore anti-tumor immunity."
Researchers have identified a compound called TRAIL-inducing Compound 10 (TIC10) as a potential solution. TIC10 stimulates the tumor suppression capabilities of TRAIL in both normal and tumor tissues, including in the brain, and induces tumor cell death in mice. They report their findings in the journal Science Translational Medicine.
TIC10 is a small molecule. This organic compound binds to a protein and alters what the protein does.
Stimulation of TRAIL protein is sustained in both tumor and normal cells, with the normal cells contributing to the TIC10-induced cancer cell death through a bystander effect. It is effective in cancer cell samples and cell lines resistant to conventional therapies.
"I was surprised and impressed that we were able to do this," El-Deiry said. "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."
New treatments are needed for advanced cancer, as more than half a million people in the United States will die of cancer in 2013.
"We have enough preclinical information to support the rationale for testing this new drug in the clinic," El-Deiry said.
TIC10 seems to be nontoxic to normal cells or mice even at doses 10 times higher that an observed therapeutic dose. However, more research needs to be completed to satisfy FDA requirements prior to initiation of clinical testing.
Other researchers are Joshua E. Allen, David T. Dicker, Akshal S. Patel, Nathan G. Dolloff, Kimberly A. Scata,Wenge Wang, all of Penn State Hershey Cancer Institute; Gabriel Krigsfeld, Patrick A. Mayes, Luv Patel, University of Pennsylvania School of Medicine; Evangelos Messaris, Department of Surgery, Penn State College Medicine; Jun-Ying Zhou and Gen Sheng Wu, Wayne State University School of Medicine.
This study was funded by the American Cancer Society, Penn State Hershey Cancer Institute and the National Institutes of Health.
Matthew Solovey | EurekAlert!
The herbivore dilemma: How corn plants fights off simultaneous attacks
09.02.2016 | Boyce Thompson Institute for Plant Research
Shedding Light on Bacteria
09.02.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
Indications of light-induced lossless electricity transmission in fullerenes contribute to the search for superconducting materials for practical applications.
Superconductors have long been confined to niche applications, due to the fact that the highest temperature at which even the best of these materials becomes...
Researchers at King’s College London and the Wellcome Trust Sanger Institute in the United Kingdom have for the first time demonstrated a direct link between the Wbp2 gene and progressive hearing loss. The scientists report that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mouse as well as in two clinical cases of children with deafness with no other obvious features. The results are published in EMBO Molecular Medicine.
The scientists have shown that hearing impairment is linked to hormonal signalling rather than to hair cell degeneration. Wbp2 is known as a transcriptional...
Pollens, the bane of allergy sufferers, could represent a boon for battery makers: Recent research has suggested their potential use as anodes in lithium-ion batteries.
"Our findings have demonstrated that renewable pollens could produce carbon architectures for anode applications in energy storage devices," said Vilas Pol, an...
Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...
09.02.2016 | Event News
02.02.2016 | Event News
26.01.2016 | Event News
09.02.2016 | Event News
09.02.2016 | Materials Sciences
09.02.2016 | Power and Electrical Engineering